Pesticidal compositions and processes related thereto

ABSTRACT

This document discloses molecules having the following formula (“Formula One”): 
                         
and processes associated therewith.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of, and claims the benefit of, U.S. patent application Ser. No. 14/132,977, which was filed on Dec. 18, 2013, the entire disclosure of which is hereby expressly incorporated by reference, and which claims the benefit of U.S. provisional patent application Ser. No. 61/739,026 filed Dec. 19, 2012, the entire disclosure of which is hereby expressly incorporated by reference.

FIELD OF THE DISCLOSURE

The invention disclosed in this document is related to the field of processes to produce molecules that are useful as pesticides (e.g., acaricides, insecticides, molluscicides, and nematicides), such molecules, and processes of using such molecules to control pests.

BACKGROUND OF THE DISCLOSURE

Pests cause millions of human deaths around the world each year. Furthermore, there are more than ten thousand species of pests that cause losses in agriculture. The world-wide agricultural losses amount to billions of U.S. dollars each year.

Termites cause damage to all kinds of private and public structures. The world-wide termite damage losses amount to billions of U.S. dollars each year.

Stored food pests eat and adulterate stored food. The world-wide stored food losses amount to billions of U.S. dollars each year, but more importantly, deprive people of needed food.

There is an acute need for new pesticides. Certain pests are developing resistance to pesticides in current use. Hundreds of pest species are resistant to one or more pesticides. The development of resistance to some of the older pesticides, such as DDT, the carbamates, and the organophosphates, is well known. But resistance has even developed to some of the newer pesticides, for example, imidacloprid.

Therefore, for many reasons, including the above reasons, a need exists for new pesticides.

DEFINITIONS

The examples given in the definitions are generally non-exhaustive and must not be construed as limiting the invention disclosed in this document. It is understood that a substituent should comply with chemical bonding rules and steric compatibility constraints in relation to the particular molecule to which it is attached.

“Alkenyl” means an acyclic, unsaturated (at least one carbon-carbon double bond), branched or unbranched, substituent consisting of carbon and hydrogen, for example, vinyl, allyl, butenyl, pentenyl, and hexenyl.

“Alkenyloxy” means an alkenyl further consisting of a carbon-oxygen single bond, for example, allyloxy, butenyloxy, pentenyloxy, hexenyloxy.

“Alkoxy” means an alkyl further consisting of a carbon-oxygen single bond, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, and tert-butoxy.

“Alkyl” means an acyclic, saturated, branched or unbranched, substituent consisting of carbon and hydrogen, for example, methyl, ethyl, (C₃)alkyl which represents n-propyl and isopropyl), (C₄)alkyl which represents n-butyl, sec-butyl, isobutyl, and tert-butyl.

“Alkynyl” means an acyclic, unsaturated (at least one carbon-carbon triple bond), branched or unbranched, substituent consisting of carbon and hydrogen, for example, ethynyl, propargyl, butynyl, and pentynyl.

“Alkynyloxy” means an alkynyl further consisting of a carbon-oxygen single bond, for example, pentynyloxy, hexynyloxy, heptynyloxy, and octynyloxy.

“Aryl” means a cyclic, aromatic substituent consisting of hydrogen and carbon, for example, phenyl, naphthyl, and biphenyl.

“(C_(x)-C_(y))” where the subscripts “x” and “y” are integers such as 1, 2, or 3, means the range of carbon atoms for a substituent—for example, (C₁-C₄)alkyl means methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, and tert-butyl, each individually.

“Cycloalkenyl” means a monocyclic or polycyclic, unsaturated (at least one carbon-carbon double bond) substituent consisting of carbon and hydrogen, for example, cyclobutenyl, cyclopentenyl, cyclohexenyl, norbomenyl, bicyclo[2.2.2]octenyl, tetrahydronaphthyl, hexahydronaphthyl, and octahydronaphthyl.

“Cycloalkenyloxy” means a cycloalkenyl further consisting of a carbon-oxygen single bond, for example, cyclobutenyloxy, cyclopentenyloxy, norbornenyloxy, and bicyclo[2.2.2]octenyloxy.

“Cycloalkyl” means a monocyclic or polycyclic, saturated substituent consisting of carbon and hydrogen, for example, cyclopropyl, cyclobutyl, cyclopentyl, norbornyl, bicyclo[2.2.2]octyl, and decahydronaphthyl.

“Cycloalkoxy” means a cycloalkyl further consisting of a carbon-oxygen single bond, for example, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, norbornyloxy, and bicyclo[2.2.2]octyloxy.

“Halo” means fluoro, chloro, bromo, and iodo.

“Haloalkoxy” means an alkoxy further consisting of, from one to the maximum possible number of identical or different, halos, for example, fluoromethoxy, trifluoromethoxy, 2,2-difluoropropoxy, chloromethoxy, trichloromethoxy, 1,1,2,2-tetrafluoroethoxy, and pentafluoroethoxy.

“Haloalkyl” means an alkyl further consisting of, from one to the maximum possible number of, identical or different, halos, for example, fluoromethyl, trifluoromethyl, 2,2-difluoropropyl, chloromethyl, trichloromethyl, and 1,1,2,2-tetrafluoroethyl.

“Heterocyclyl” means a cyclic substituent that may be fully saturated, partially unsaturated, or fully unsaturated, where the cyclic structure contains at least one carbon and at least one heteroatom, where said heteroatom is nitrogen, sulfur, or oxygen. In the case of sulfur, that atom can be in other oxidation states such as a sulfoxide and sulfone. Examples of aromatic heterocyclyls include, but are not limited to, benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzothienyl, benzothiazolyl, cinnolinyl, furanyl, imidazolyl, indazolyl, indolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl, triazinyl, and triazolyl. Examples of fully saturated heterocyclyls include, but are not limited to, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, oxetanyl, tetrahydrofuranyl, tetrahydrothienyl and tetrahydropyranyl. Examples of partially unsaturated heterocyclyls include, but are not limited to, 1,2,3,4-tetrahydroquinolinyl, 4,5-dihydro-oxazolyl, 4,5-dihydro-1H-pyrazolyl, 4,5-dihydro-isoxazolyl, and 2,3-dihydro-[1,3,4]-oxadiazolyl.

Additional examples include the following

DETAILED DESCRIPTION OF THE DISCLOSURE

This document discloses molecules having the following formula (“Formula One”):

wherein:

(a) R1 is selected from

-   -   (1) H, F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl,         (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy, S(C₁-C₈)alkyl,         S(halo(C₁-C₈)alkyl), S(O)(C₁-C₈)alkyl, S(O)(halo(C₁-C₈)alkyl),         S(O)₂(C₁-C₈)alkyl, S(O)₂(halo(C₁-C₈)alkyl), N(R14)(R15),     -   (2) substituted (C₁-C₈)alkyl, wherein said substituted         (C₁-C₈)alkyl has one or more substituents selected from CN and         NO₂,     -   (3) substituted halo(C₁-C₈)alkyl, wherein said substituted         halo(C₁-C₈)alkyl, has one or more substituents selected from CN         and NO₂,     -   (4) substituted (C₁-C₈)alkoxy, wherein said substituted         (C₁-C₈)alkoxy has one or more substituents selected from CN and         NO₂, and     -   (5) substituted halo(C₁-C₈)alkoxy, wherein said substituted         halo(C₁-C₈)alkoxy has one or more substituents selected from CN         and NO₂;

(b) R2 is selected from

-   -   (1) H, F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl,         (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy, S(C₁-C₈)alkyl,         S(halo(C₁-C₈)alkyl), S(O)(C₁-C₈)alkyl, S(O)(halo(C₁-C₈)alkyl),         S(O)₂(C₁-C₈)alkyl, S(O)₂(halo(C₁-C₈)alkyl), N(R14)(R15),     -   (2) substituted (C₁-C₈)alkyl, wherein said substituted         (C₁-C₈)alkyl has one or more substituents selected from CN and         NO₂,     -   (3) substituted halo(C₁-C₈)alkyl, wherein said substituted         halo(C₁-C₈)alkyl, has one or more substituents selected from CN         and NO₂,     -   (4) substituted (C₁-C₈)alkoxy, wherein said substituted         (C₁-C₈)alkoxy has one or more substituents selected from CN and         NO₂, and     -   (5) substituted halo(C₁-C₈)alkoxy, wherein said substituted         halo(C₁-C₈)alkoxy has one or more substituents selected from CN         and NO₂;

(c) R3 is selected from

-   -   (1) H, F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl,         (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy, S(C₁-C₈)alkyl,         S(halo(C₁-C₈)alkyl), S(O)(C₁-C₈)alkyl, S(O)(halo(C₁-C₈)alkyl),         S(O)₂(C₁-C₈)alkyl, S(O)₂(halo(C₁-C₈)alkyl), N(R14)(R15),     -   (2) substituted (C₁-C₈)alkyl, wherein said substituted         (C₁-C₈)alkyl has one or more substituents selected from CN and         NO₂,     -   (3) substituted halo(C₁-C₈)alkyl, wherein said substituted         halo(C₁-C₈)alkyl, has one or more substituents selected from CN         and NO₂,     -   (4) substituted (C₁-C₈)alkoxy, wherein said substituted         (C₁-C₈)alkoxy has one or more substituents selected from CN and         NO₂, and     -   (5) substituted halo(C₁-C₈)alkoxy, wherein said substituted         halo(C₁-C₈)alkoxy has one or more substituents selected from CN         and NO₂;

(d) R4 is selected from

-   -   (1) H, F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl,         (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy, S(C₁-C₈)alkyl,         S(halo(C₁-C₈)alkyl), S(O)(C₁-C₈)alkyl, S(O)(halo(C₁-C₈)alkyl),         S(O)₂(C₁-C₈)alkyl, S(O)₂(halo(C₁-C₈)alkyl), N(R14)(R15),     -   (2) substituted (C₁-C₈)alkyl, wherein said substituted         (C₁-C₈)alkyl has one or more substituents selected from CN and         NO₂,     -   (3) substituted halo(C₁-C₈)alkyl, wherein said substituted         halo(C₁-C₈)alkyl, has one or more substituents selected from CN         and NO₂,     -   (4) substituted (C₁-C₈)alkoxy, wherein said substituted         (C₁-C₈)alkoxy has one or more substituents selected from CN and         NO₂, and     -   (5) substituted halo(C₁-C₈)alkoxy, wherein said substituted         halo(C₁-C₈)alkoxy has one or more substituents selected from CN         and NO₂;

(e) R5 is selected from

-   -   (1) H, F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl,         (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy, S(C₁-C₈)alkyl,         S(halo(C₁-C₈)alkyl), S(O)(C₁-C₈)alkyl, S(O)(halo(C₁-C₈)alkyl),         S(O)₂(C₁-C₈)alkyl, S(O)₂(halo(C₁-C₈)alkyl), N(R14)(R15),     -   (2) substituted (C₁-C₈)alkyl, wherein said substituted         (C₁-C₈)alkyl has one or more substituents selected from CN and         NO₂,     -   (3) substituted halo(C₁-C₈)alkyl, wherein said substituted         halo(C₁-C₈)alkyl, has one or more substituents selected from CN         and NO₂,     -   (4) substituted (C₁-C₈)alkoxy, wherein said substituted         (C₁-C₈)alkoxy has one or more substituents selected from CN and         NO₂, and     -   (5) substituted halo(C₁-C₈)alkoxy, wherein said substituted         halo(C₁-C₈)alkoxy has one or more substituents selected from CN         and NO₂;

(f) R6 is a (C₁-C₈)haloalkyl;

(g) R7 is selected from H, F, Cl, Br, I, OH, (C₁-C₈)alkoxy, and halo(C₁-C₈)alkoxy;

(h) R8 is selected from H, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl, OR14, and N(R14)(R15);

(i) R9 is selected from H, F, Cl, Br, I, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy, OR14, and N(R14)(R15);

(j) R10 is selected from

-   -   (1) H, F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl,         (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy, cyclo(C₃-C₆)alkyl,         S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), S(O)(C₁-C₈)alkyl,         S(O)(halo(C₁-C₈)alkyl), S(O)₂(C₁-C₈)alkyl,         S(O)₂(halo(C₁-C₈)alkyl), NR14R15, C(═O)H, C(═O)N(R14)(R15),         CN(R14)(R15)(═NOH), (C═O)O(C₁-C₈)alkyl, (C═O)OH, heterocyclyl,         (C₂-C₈)alkenyl, halo(C₂-C₈)alkenyl, (C₂-C₈)alkynyl,     -   (2) substituted (C₁-C₈)alkyl, wherein said substituted         (C₁-C₈)alkyl has one or more substituents selected from OH,         (C₁-C₈)alkoxy, S(C₁-C₈)alkyl, S(O)(C₁-C₈)alkyl,         S(O)₂(C₁-C₈)alkyl, NR14R15, and     -   (3) substituted halo(C₁-C₈)alkyl, wherein said substituted         halo(C₁-C₈)alkyl, has one or more substituents selected from         (C₁-C₈)alkoxy, S(C₁-C₈)alkyl, S(O)(C₁-C₈)alkyl,         S(O)₂(C₁-C₈)alkyl, and N(R14)(R15);

(k) R11 is (C═X5)N(X6)(R14) wherein

-   -   X5 is selected from O, S, or NH, and     -   X6 is selected from halocyclo(C₃-C₆) alkyl, substituted         cyclo(C₃-C₆) alkyl, and substituted halocyclo(C₃-C₆) alkyl,     -   wherein said substituted cyclo(C₃-C₆) alkyl is substituted with         one or more substituents selected from CN, NO₂, (C₁-C₈)alkyl,         (C₂-C₈)alkenyl, (C₂-C₈)alkynyl, halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy,         cyclo(C₃-C₆)alkyl, aryl, substituted-aryl, (C₁-C₈)alkyl-aryl,         (C₁-C₈)alkyl-(substituted-aryl), O—(C₁-C₈)alkyl-aryl,         O—(C₁-C₈)alkyl-(substituted-aryl), heterocyclyl,         substituted-heterocyclyl, (C₁-C₈)alkyl-heterocyclyl,         (C₁-C₈)alkyl-(substituted-heterocyclyl),         O—(C₁-C₈)alkyl-heterocyclyl,         O—(C₁-C₈)alkyl-(substituted-heterocyclyl), N(R15)(R16),         C(═X5)N(R15)(R16), (C₁-C₈)alkyl-C(═X5)N(R15)(R16),         C(═O)(C₁-C₈)alkyl, C(═O)(halo(C₁-C₈)alkyl),         C(═O)(C₃-C₆)cycloalkyl, (C₁-C₈)alkyl-C(═O)O(C₁-C₈)alkyl, and         C(═O)H, and     -   wherein said substituted halocyclo(C₃-C₆) alkyl is substituted         with one or more substituents selected from CN, NO₂,         (C₁-C₈)alkyl, (C₂-C₈)alkenyl, (C₂-C₈)alkynyl, halo(C₁-C₈)alkyl,         (C₁-C₈)alkoxy, cyclo(C₃-C₆)alkyl, aryl, substituted-aryl,         (C₁-C₈)alkyl-aryl, (C₁-C₈)alkyl-(substituted-aryl),         O—(C₁-C₈)alkyl-aryl, O—(C₁-C₈)alkyl-(substituted-aryl),         heterocyclyl, substituted-heterocyclyl,         (C₁-C₈)alkyl-heterocyclyl,         (C₁-C₈)alkyl-(substituted-heterocyclyl),         O—(C₁-C₈)alkyl-heterocyclyl,         O—(C₁-C₈)alkyl-(substituted-heterocyclyl), N(R15)(R16),         C(═X5)N(R15)(R16), (C₁-C₈)alkyl-C(═X5)N(R15)(R16),         C(═O)(C₁-C₈)alkyl, C(═O)(halo(C₁-C₈)alkyl),         C(═O)(C₃-C₆)cycloalkyl, (C₁-C₈)alkyl-C(═O)O(C₁-C₈)alkyl, and         C(═O)H,     -   wherein each said substituted aryl has one or more substituents         selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,         halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,         S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈)alkyl)₂ (wherein         each (C₁-C₈)alkyl is independently selected), and oxo, and     -   wherein each said substituted heterocyclyl has one or more         substituents selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,         halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,         S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈)alkyl)₂ (wherein         each (C₁-C₈)alkyl is independently selected), C(═O)(C₁-C₈)alkyl,         C(═O)(C₃-C₆)cycloalkyl, S(═O)₂(C₁-C₈)alkyl, NR14R15, and oxo;

(l) R12 is selected from (v), H, F, Cl, Br, I, CN, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy, and cyclo(C₃-C₆)alkyl;

(m) R13 is selected from (v), H, F, Cl, Br, I, CN, (C₁-C₈)alkyl, halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, and halo(C₁-C₈)alkoxy;

(n) each R14 is independently selected from H, (C₁-C₈)alkyl, (C₂-C₈)alkenyl, substituted (C₁-C₈)alkyl, halo(C₁-C₈)alkyl, substituted halo(C₁-C₈)alkyl), (C₁-C₈)alkoxy, cyclo(C₃-C₆)alkyl, aryl, substituted-aryl, (C₁-C₈)alkyl-aryl, (C₁-C₈)alkyl-(substituted-aryl), O—(C₁-C₈)alkyl-aryl, O—(C₁-C₈)alkyl-(substituted-aryl), heterocyclyl, substituted-heterocyclyl, (C₁-C₈)alkyl-heterocyclyl, (C₁-C₈)alkyl-(substituted-heterocyclyl), O—(C₁-C₈)alkyl-heterocyclyl, O—(C₁-C₈)alkyl-(substituted-heterocyclyl), N(R16)(R17), (C₁-C₈)alkyl-C(═O)N(R16)(R17), C(═O)(C₁-C₈)alkyl, C(═O)(halo(C₁-C₈)alkyl), C(═O)(C₃-C₆)cycloalkyl, (C₁-C₈)alkyl-C(═O)O(C₁-C₈)alkyl, C(═O)H

-   -   wherein each said substituted (C₁-C₈)alkyl has one or more         substituents selected from CN, and NO₂,     -   wherein each said substituted halo(C₁-C₈)alkyl), has one or more         substituents selected from CN, and NO₂,     -   wherein each said substituted-aryl has one or more substituents         selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,         halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,         S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈)alkyl)₂ (wherein         each (C₁-C₈)alkyl is independently selected), and oxo, and     -   wherein each said substituted-heterocyclyl has one or more         substituents selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,         halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,         (C₃-C₆)cycloalkyl S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl),         N((C₁-C₈)alkyl)₂ (wherein each (C₁-C₈)alkyl is independently         selected), heterocyclyl, C(═O)(C₁-C₈)alkyl, C(═O)O(C₁-C₈)alkyl,         and oxo, (wherein said alkyl, alkoxy, and heterocyclyl, may be         further substituted with one or more of F, Cl, Br, I, CN, and         NO₂);

(o) each R15 is independently selected from H, (C₁-C₈)alkyl, (C₂-C₈)alkenyl, substituted (C₁-C₈)alkyl, halo(C₁-C₈)alkyl, substituted halo(C₁-C₈)alkyl), (C₁-C₈)alkoxy, cyclo(C₃-C₆)alkyl, aryl, substituted-aryl, (C₁-C₈)alkyl-aryl, (C₁-C₈)alkyl-(substituted-aryl), O—(C₁-C₈)alkyl-aryl, O—(C₁-C₈)alkyl-(substituted-aryl), heterocyclyl, substituted-heterocyclyl, (C₁-C₈)alkyl-heterocyclyl, (C₁-C₈)alkyl-(substituted-heterocyclyl), O—(C₁-C₈)alkyl-heterocyclyl, O—(C₁-C₈)alkyl-(substituted-heterocyclyl), N(R16)(R17), (C₁-C₈)alkyl-C(═O)N(R16)(R17), C(═O)(C₁-C₈)alkyl, C(═O)(halo(C₁-C₈)alkyl), C(═O)(C₃-C₆)cycloalkyl, (C₁-C₈)alkyl-C(═O)O(C₁-C₈)alkyl, C(═O)H

-   -   wherein each said substituted (C₁-C₈)alkyl has one or more         substituents selected from CN, and NO₂,     -   wherein each said substituted halo(C₁-C₈)alkyl), has one or more         substituents selected from CN, and NO₂,     -   wherein each said substituted-aryl has one or more substituents         selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,         halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,         S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈)alkyl)₂ (wherein         each (C₁-C₈)alkyl is independently selected), and oxo, and     -   wherein each said substituted-heterocyclyl has one or more         substituents selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,         halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,         (C₃-C₆)cycloalkyl S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl),         N((C₁-C₈)alkyl)₂ (wherein each (C₁-C₈)alkyl is independently         selected), heterocyclyl, C(═O)(C₁-C₈)alkyl, C(═O)O(C₁-C₈)alkyl,         and oxo, (wherein said alkyl, alkoxy, and heterocyclyl, may be         further substituted with one or more of F, Cl, Br, I, CN, and         NO₂);

(p) each R16 is independently selected from H, (C₁-C₈)alkyl, substituted-(C₁-C₈)alkyl, halo(C₁-C₈)alkyl, substituted-halo(C₁-C₈)alkyl, cyclo(C₃-C₆)alkyl, aryl, substituted-aryl, (C₁-C₈)alkyl-aryl, (C₁-C₈)alkyl-(substituted-aryl), O—(C₁-C₈)alkyl-aryl, O—(C₁-C₈)alkyl-(substituted-aryl), heterocyclyl, substituted-heterocyclyl, (C₁-C₈)alkyl-heterocyclyl, (C₁-C₈)alkyl-(substituted-heterocyclyl), O—(C₁-C₈)alkyl-heterocyclyl, O—(C₁-C₈)alkyl-(substituted-heterocyclyl), O—(C₁-C₈)alkyl

-   -   wherein each said substituted (C₁-C₈)alkyl has one or more         substituents selected from CN, and NO₂,     -   wherein each said substituted halo(C₁-C₈)alkyl), has one or more         substituents selected from CN, and NO₂,     -   wherein each said substituted-aryl has one or more substituents         selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,         halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,         S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈) alkyl)₂ (wherein         each (C₁-C₈)alkyl is independently selected), and oxo, and     -   wherein each said substituted-heterocyclyl has one or more         substituents selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,         halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈) alkoxy,         S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈)alkyl)₂ (wherein         each (C₁-C₈)alkyl is independently selected), and oxo;

(q) each R17 is independently selected from H, (C₁-C₈)alkyl, substituted-(C₁-C₈)alkyl, halo(C₁-C₈)alkyl, substituted-halo(C₁-C₈)alkyl, cyclo(C₃-C₆)alkyl, aryl, substituted-aryl, (C₁-C₈)alkyl-aryl, (C₁-C₈)alkyl-(substituted-aryl), O—(C₁-C₈)alkyl-aryl, O—(C₁-C₈)alkyl-(substituted-aryl), heterocyclyl, substituted-heterocyclyl, (C₁-C₈)alkyl-heterocyclyl, (C₁-C₈)alkyl-(substituted-heterocyclyl), O—(C₁-C₈)alkyl-heterocyclyl, O—(C₁-C₈)alkyl-(substituted-heterocyclyl), O—(C₁-C₈)alkyl

-   -   wherein each said substituted (C₁-C₈)alkyl has one or more         substituents selected from CN, and NO₂,     -   wherein each said substituted halo(C₁-C₈)alkyl), has one or more         substituents selected from CN, and NO₂,     -   wherein each said substituted-aryl has one or more substituents         selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,         halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈)alkoxy,         S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈) alkyl)₂ (wherein         each (C₁-C₈)alkyl is independently selected), and oxo, and     -   wherein each said substituted-heterocyclyl has one or more         substituents selected from F, Cl, Br, I, CN, NO₂, (C₁-C₈)alkyl,         halo(C₁-C₈)alkyl, (C₁-C₈)alkoxy, halo(C₁-C₈) alkoxy,         S(C₁-C₈)alkyl, S(halo(C₁-C₈)alkyl), N((C₁-C₈)alkyl)₂ (wherein         each (C₁-C₈)alkyl is independently selected), and oxo;

(r) X1 is selected from N and CR12;

(s) X2 is selected from N, CR9, and CR13;

(t) X3 is selected from N and CR9; and

(v) R12 and R13 together form a linkage containing 3 to 4 atoms selected from C, N, O, and S, wherein said linkage connects back to the ring to form a 5 to 6 member saturated or unsaturated cyclic ring, wherein said linkage has at least one substituent X4 wherein X4 is selected from R14, N(R14)(R15), N(R14)(C(═O)R14), N(R14)(C(═S)R14), N(R14)(C(═O)N(R14)(R14)), N(R14)(C(═S)N(R14)(R14)), N(R14)(C(═O)N(R14)((C₂-C₈)alkenyl)), N(R14)(C(═S)N(R14)((C₂-C₈)alkenyl)), wherein each R14 is independently selected.

In another embodiment of this invention R1 may be selected from any combination of one or more of the following—H, F, Cl, Br, I, CN, NO₂, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (C₅)alkoxy, (C₆)alkoxy, (C₇)alkoxy, (C₈)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(C₅)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy. This embodiment also may be combined with any of the subsequent embodiments.

In another embodiment of this invention R2 may be selected from any combination of one or more of the following—H, F, Cl, Br, I, CN, NO₂, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (C₅)alkoxy, (C₆)alkoxy, (C₇)alkoxy, (C₈)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(C₅)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R3 may be selected from any combination of one or more of the following—H, F, Cl, Br, I, CN, NO₂, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (C₅)alkoxy, (C₆)alkoxy, (C₇)alkoxy, (C₈)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(C₅)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R4 may be selected from any combination of one or more of the following—H, F, Cl, Br, I, CN, NO₂, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (C₅)alkoxy, (C₆)alkoxy, (C₇)alkoxy, (C₈)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(C₅)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R5 may be selected from any combination of one or more of the following—H, F, Cl, Br, I, CN, NO₂, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (C₅)alkoxy, (C₆)alkoxy, (C₇)alkoxy, (C₈)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(C₅)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R2 and R4 are selected from F, Cl, Br, I, CN, and NO₂ and R1, R3, and R5 are H. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R2, R3, and R4 are selected from F, Cl, Br, I, CN, and NO₂ and R1, and R5 are H. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R2, R3, and R4 are independently selected from F and Cl and R1 and R5 are H. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R1 is selected from Cl and H. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R2 is selected from CF₃, CH₃, Cl, F, and H. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R3 is selected from OCH₃, CH₃, F, Cl, or H. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R4 is selected from CF₃, CH₃, Cl, F, and H. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R5 is selected from F, Cl, and H. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R6 may be selected from any combination of one or more of the following—halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, and halo(C₈)alkyl. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R6 is trifluoromethyl. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R7 may be selected from any combination of one or more of the following—H, F, Cl, Br, and I. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R7 is selected from H, OCH₃, and OH. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R8 may be selected from any combination of one or more of the following—H, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, and halo(C₈)alkyl. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R8 is selected from CH₃ and H. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R9 may be selected from any combination of one or more of the following—H, F, Cl, Br, I, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (C₅)alkoxy, (C₆)alkoxy, (C₇)alkoxy, (C₈)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(C₅)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R10 may be selected from any combination of one or more of the following—H, F, Cl, Br, I, CN, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (C₅)alkoxy, (C₆)alkoxy, (C₇)alkoxy, (C₈)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(C₅)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, halo(C₈)alkoxy, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R10 may be selected from any combination of one or more of the following—H, Cl, Br, CH₃, and CF₃. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R10 is selected from Br, C(═NOH)NH₂, C(═O)H, C(═O)NH₂, C(═O)OCH₂CH₃, C(═O)OH, CF₃, CH₂CH₃, CH₂OH, CH3, Cl, CN, F, H, NH₂, NHC(═O)H, NHCH₃, NO₂, OCH₃, OCHF₂, and pyridyl. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R11 may be selected from any combination of one or more of the following—(C═O)N(H)(cyclopropyl-(C═O)N(H)(CH₂CF₃)), (C═O)N(H)(cyclopropyl-(C═S)N(H)(CH₂CF₃)), (C═O)N(H)(cyclobutyl-(C═O)N(H)(CH₂CF₃)), (C═O)N(H)(cyclopropyl-CN), and (C═O)N(H)(difluorocyclopropyl). This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R11 may be selected from any combination of one or more of the following—(C═(O or S)N(H)(cyclopropyl-(C═(O or S))N(H)(halo(C₁-C₆)alkyl)), (C═(O or S)N(H)(cyclobutyl-(C═(O or S))N(H)(halo(C₁-C₆)alkyl)), and (C═(O or S)N(H)(cyclopropyl-(C═(O or S))N(H)(C₁-C₆)alkyl). This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R12 may be selected from any combination of one or more of the following—H, F, Cl, Br, I, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(C₅)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R12 is selected from CH3, and H.

In another embodiment of this invention R13 may be selected from any combination of one or more of the following—H, F, Cl, Br, I, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(C₅)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R13 is selected from CH₃, Cl and H. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R12-R13 are a hydrocarbyl linkage containing CH═CHCH═CH. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R14 may be selected from any combination of one or more of the following—H, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methyl-aryl, ethyl-aryl, (C₃)alkyl-aryl, (C₄)alkyl-aryl, (C₅)alkyl-aryl, (C₆)alkyl-aryl, (C₇)alkyl-aryl, (C₈)alkyl-aryl, methyl-(substituted-aryl), ethyl-(substituted-aryl), (C₃)alkyl-(substituted-aryl), (C₄)alkyl-(substituted-aryl), (C₅)alkyl-(substituted-aryl), (C₆)alkyl-(substituted-aryl), (C₇)alkyl-(substituted-aryl), (C₈)alkyl-(substituted-aryl), O-methyl-aryl, O-ethyl-aryl, O—(C₃)alkyl-aryl, O—(C₄)alkyl-aryl, O—(C₅)alkyl-aryl, O—(C₆)alkyl-aryl, O—(C₇)alkyl-aryl, O—(C₈)alkyl-aryl, O-methyl-(substituted-aryl), O-ethyl-(substituted-aryl), O—(C₃)alkyl-(substituted-aryl), O—(C₄)alkyl-(substituted-aryl), O—(C₅)alkyl-(substituted-aryl), O—(C₆)alkyl-(substituted-aryl), O—(C₇)alkyl-(substituted-aryl), O—(C₈)alkyl-(substituted-aryl), methyl-heterocyclyl, ethyl-heterocyclyl, (C₃)alkyl-heterocyclyl, (C₄)alkyl-heterocyclyl, (C₅)alkyl-heterocyclyl, (C₆)alkyl-heterocyclyl, (C₇)alkyl-heterocyclyl, (C₈)alkyl-heterocyclyl, methyl-(substituted-heterocyclyl), ethyl-(substituted-heterocyclyl), (C₃)alkyl-(substituted-heterocyclyl), (C₄)alkyl-(substituted-heterocyclyl), (C₅)alkyl-(substituted-heterocyclyl), (C₆)alkyl-(substituted-heterocyclyl), (C₇)alkyl-(substituted-heterocyclyl), (C₈)alkyl-(substituted-heterocyclyl), O-methyl-heterocyclyl, O-ethyl-heterocyclyl, O—(C₃)alkyl-heterocyclyl, O—(C₄)alkyl-heterocyclyl, O—(C₅)alkyl-heterocyclyl, O—(C₆)alkyl-heterocyclyl, O—(C₇)alkyl-heterocyclyl, O—(C₈)alkyl-heterocyclyl, O-methyl-(substituted-heterocyclyl), O-ethyl-(substituted-heterocyclyl), O—(C₃)alkyl-(substituted-heterocyclyl), O—(C₄)alkyl-(substituted-heterocyclyl), O—(C₅)alkyl-(substituted-heterocyclyl), O—(C₆)alkyl-(substituted-heterocyclyl), O—(C₇)alkyl-(substituted-heterocyclyl), O—(C₈)alkyl-(substituted-heterocyclyl), methyl-C(═O)N(R16)(R17), ethyl-C(═O)N(R16)(R17), (C₃)alkyl-C(═O)N(R16)(R17), (C₄)alkyl-C(═O)N(R16)(R17), (C₅)alkyl-C(═O)N(R16)(R17), (C₆)alkyl-C(═O)N(R16)(R17), (C₇)alkyl-C(═O)N(R16)(R17), and (C₈)alkyl-C(═O)N(R16)(R17). This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R14 may be selected from any combination of one or more of the following—H, CH₃, CH₂CF₃, CH₂-halopyridyl, oxo-pyrrolidinyl, halophenyl, thietanyl, CH₂-phenyl, CH₂-pyridyl, thietanyl-dioxide, CH₂-halothiazolyl, C((CH₃)₂)-pyridyl, N(H)(halophenyl), CH₂-pyrimidinyl, CH₂-tetrahydrofuranyl, CH₂-furanyl, O—CH₂-halopyridyl, and CH₂C(═O)N(H)(CH₂CF₃). This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R15 may be selected from any combination of one or more of the following—H, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methyl-aryl, ethyl-aryl, (C₃)alkyl-aryl, (C₄)alkyl-aryl, (C₅)alkyl-aryl, (C₆)alkyl-aryl, (C₇)alkyl-aryl, (C₈)alkyl-aryl, methyl-(substituted-aryl), ethyl-(substituted-aryl), (C₃)alkyl-(substituted-aryl), (C₄)alkyl-(substituted-aryl), (C₅)alkyl-(substituted-aryl), (C₆)alkyl-(substituted-aryl), (C₇)alkyl-(substituted-aryl), (C₈)alkyl-(substituted-aryl), O-methyl-aryl, O-ethyl-aryl, O—(C₃)alkyl-aryl, O—(C₄)alkyl-aryl, O—(C₅)alkyl-aryl, O—(C₆)alkyl-aryl, O—(C₇)alkyl-aryl, O—(C₈)alkyl-aryl, O-methyl-(substituted-aryl), O-ethyl-(substituted-aryl), O—(C₃)alkyl-(substituted-aryl), O—(C₄)alkyl-(substituted-aryl), O—(C₅)alkyl-(substituted-aryl), O—(C₆)alkyl-(substituted-aryl), O—(C₇)alkyl-(substituted-aryl), O—(C₈)alkyl-(substituted-aryl), methyl-heterocyclyl, ethyl-heterocyclyl, (C₃)alkyl-heterocyclyl, (C₄)alkyl-heterocyclyl, (C₅)alkyl-heterocyclyl, (C₆)alkyl-heterocyclyl, (C₇)alkyl-heterocyclyl, (C₈)alkyl-heterocyclyl, methyl-(substituted-heterocyclyl), ethyl-(substituted-heterocyclyl), (C₃)alkyl-(substituted-heterocyclyl), (C₄)alkyl-(substituted-heterocyclyl), (C₅)alkyl-(substituted-heterocyclyl), (C₆)alkyl-(substituted-heterocyclyl), (C₇)alkyl-(substituted-heterocyclyl), (C₈)alkyl-(substituted-heterocyclyl), O-methyl-heterocyclyl, O-ethyl-heterocyclyl, O—(C₃)alkyl-heterocyclyl, O—(C₄)alkyl-heterocyclyl, O—(C₅)alkyl-heterocyclyl, O—(C₆)alkyl-heterocyclyl, O—(C₇)alkyl-heterocyclyl, O—(C₈)alkyl-heterocyclyl, O-methyl-(substituted-heterocyclyl), O-ethyl-(substituted-heterocyclyl), O—(C₃)alkyl-(substituted-heterocyclyl), O—(C₄)alkyl-(substituted-heterocyclyl), O—(C₅)alkyl-(substituted-heterocyclyl), O—(C₆)alkyl-(substituted-heterocyclyl), O—(C₇)alkyl-(substituted-heterocyclyl), O—(C₈)alkyl-(substituted-heterocyclyl), methyl-C(═O)N(R16)(R17), ethyl-C(═O)N(R16)(R17), (C₃)alkyl-C(═O)N(R16)(R17), (C₄)alkyl-C(═O)N(R16)(R17), (C₅)alkyl-C(═O)N(R16)(R17), (C₆)alkyl-C(═O)N(R16)(R17), (C₇)alkyl-C(═O)N(R16)(R17), and (C₈)alkyl-C(═O)N(R16)(R17). This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R15 may be selected from any combination of one or more of the following—H, CH₃, CH₂CF₃, CH₂-halopyridyl, oxo-pyrrolidinyl, halophenyl, thietanyl, CH₂-phenyl, CH₂-pyridyl, thietanyl-dioxide, CH₂-halothiazolyl, C((CH₃)₂)-pyridyl, N(H)(halophenyl), CH₂-pyrimidinyl, CH₂-tetrahydrofuranyl, CH₂-furanyl, O—CH₂-halopyridyl, and CH₂C(═O)N(H)(CH₂CF₃). This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R16 may be selected from any combination of one or more of the following—H, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methyl-aryl, ethyl-aryl, (C₃)alkyl-aryl, (C₄)alkyl-aryl, (C₅)alkyl-aryl, (C₆)alkyl-aryl, (C₇)alkyl-aryl, (C₈)alkyl-aryl, methyl-(substituted-aryl), ethyl-(substituted-aryl), (C₃)alkyl-(substituted-aryl), (C₄)alkyl-(substituted-aryl), (C₅)alkyl-(substituted-aryl), (C₆)alkyl-(substituted-aryl), (C₇)alkyl-(substituted-aryl), (C₈)alkyl-(substituted-aryl), O-methyl-aryl, O-ethyl-aryl, O—(C₃)alkyl-aryl, O—(C₄)alkyl-aryl, O—(C₅)alkyl-aryl, O—(C₆)alkyl-aryl, O—(C₇)alkyl-aryl, O—(C₈)alkyl-aryl, O-methyl-(substituted-aryl), O-ethyl-(substituted-aryl), O—(C₃)alkyl-(substituted-aryl), O—(C₄)alkyl-(substituted-aryl), O—(C₅)alkyl-(substituted-aryl), O—(C₆)alkyl-(substituted-aryl), O—(C₇)alkyl-(substituted-aryl), O—(C₈)alkyl-(substituted-aryl), methyl-heterocyclyl, ethyl-heterocyclyl, (C₃)alkyl-heterocyclyl, (C₄)alkyl-heterocyclyl, (C₅)alkyl-heterocyclyl, (C₆)alkyl-heterocyclyl, (C₇)alkyl-heterocyclyl, (C₈)alkyl-heterocyclyl, methyl-(substituted-heterocyclyl), ethyl-(substituted-heterocyclyl), (C₃)alkyl-(substituted-heterocyclyl), (C₄)alkyl-(substituted-heterocyclyl), (C₅)alkyl-(substituted-heterocyclyl), (C₆)alkyl-(substituted-heterocyclyl), (C₇)alkyl-(substituted-heterocyclyl), (C₈)alkyl-(substituted-heterocyclyl), O-methyl-heterocyclyl, O-ethyl-heterocyclyl, O—(C₃)alkyl-heterocyclyl, O—(C₄)alkyl-heterocyclyl, O—(C₅)alkyl-heterocyclyl, O—(C₆)alkyl-heterocyclyl, O—(C₇)alkyl-heterocyclyl, O—(C₈)alkyl-heterocyclyl, O-methyl-(substituted-heterocyclyl), O-ethyl-(substituted-heterocyclyl), O—(C₃)alkyl-(substituted-heterocyclyl), O—(C₄)alkyl-(substituted-heterocyclyl), O—(C₅)alkyl-(substituted-heterocyclyl), O—(C₆)alkyl-(substituted-heterocyclyl), O—(C₇)alkyl-(substituted-heterocyclyl), and O—(C₈)alkyl-(substituted-heterocyclyl). This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R16 may be selected from any combination of one or more of the following—H, CH₂CF₃, cyclopropyl, thietanyl, thietanyl dioxide, and halophenyl. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R17 may be selected from any combination of one or more of the following—H, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methyl-aryl, ethyl-aryl, (C₃)alkyl-aryl, (C₄)alkyl-aryl, (C₅)alkyl-aryl, (C₆)alkyl-aryl, (C₇)alkyl-aryl, (C₈)alkyl-aryl, methyl-(substituted-aryl), ethyl-(substituted-aryl), (C₃)alkyl-(substituted-aryl), (C₄)alkyl-(substituted-aryl), (C₅)alkyl-(substituted-aryl), (C₆)alkyl-(substituted-aryl), (C₇)alkyl-(substituted-aryl), (C₈)alkyl-(substituted-aryl), O-methyl-aryl, O-ethyl-aryl, O—(C₃)alkyl-aryl, O—(C₄)alkyl-aryl, O—(C₅)alkyl-aryl, O—(C₆)alkyl-aryl, O—(C₇)alkyl-aryl, O—(C₈)alkyl-aryl, O-methyl-(substituted-aryl), O-ethyl-(substituted-aryl), O—(C₃)alkyl-(substituted-aryl), O—(C₄)alkyl-(substituted-aryl), O—(C₅)alkyl-(substituted-aryl), O—(C₆)alkyl-(substituted-aryl), O—(C₇)alkyl-(substituted-aryl), O—(C₈)alkyl-(substituted-aryl), methyl-heterocyclyl, ethyl-heterocyclyl, (C₃)alkyl-heterocyclyl, (C₄)alkyl-heterocyclyl, (C₅)alkyl-heterocyclyl, (C₆)alkyl-heterocyclyl, (C₇)alkyl-heterocyclyl, (C₈)alkyl-heterocyclyl, methyl-(substituted-heterocyclyl), ethyl-(substituted-heterocyclyl), (C₃)alkyl-(substituted-heterocyclyl), (C₄)alkyl-(substituted-heterocyclyl), (C₅)alkyl-(substituted-heterocyclyl), (C₆)alkyl-(substituted-heterocyclyl), (C₇)alkyl-(substituted-heterocyclyl), (C₈)alkyl-(substituted-heterocyclyl), O-methyl-heterocyclyl, O-ethyl-heterocyclyl, O—(C₃)alkyl-heterocyclyl, O—(C₄)alkyl-heterocyclyl, O—(C₅)alkyl-heterocyclyl, O—(C₆)alkyl-heterocyclyl, O—(C₇)alkyl-heterocyclyl, O—(C₈)alkyl-heterocyclyl, O-methyl-(substituted-heterocyclyl), O-ethyl-(substituted-heterocyclyl), O—(C₃)alkyl-(substituted-heterocyclyl), O—(C₄)alkyl-(substituted-heterocyclyl), O—(C₅)alkyl-(substituted-heterocyclyl), O—(C₆)alkyl-(substituted-heterocyclyl), O—(C₇)alkyl-(substituted-heterocyclyl), and O—(C₈)alkyl-(substituted-heterocyclyl). This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention R17 may be selected from any combination of one or more of the following—H, CH₂CF₃, cyclopropyl, thietanyl, thietanyl dioxide, and halophenyl. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention X1 is CR12, X2 is CR13, and X3 is CR9. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

In another embodiment of this invention a heterocyclyl has preferably about 6 to 10 atoms in the ring structure, more preferably, 6 to 8 atoms. This embodiment also may be combined with any of the preceding embodiments or subsequent embodiments.

The molecules of Formula One will generally have a molecular mass of about 100 Daltons to about 1200 Daltons. However, it is generally preferred if the molecular mass is from about 120 Daltons to about 900 Daltons, and it is even more generally preferred if the molecular mass is from about 140 Daltons to about 600 Daltons.

The benzyl alcohol of Formula IV, wherein R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, can be synthesized in two ways. One way, disclosed in step a of Scheme I, is by treatment of the ketone of Formula II, wherein R1, R2, R3, R4, R5, and R6 are as previously disclosed, with a reducing agent, such as sodium borohydride (NaBH₄), under basic conditions, such as aqueous sodium hydroxide (NaOH), in a polar protic solvent, such as methyl alcohol (CH₃OH) at 0° C. Alternatively, an aldehyde of Formula III, wherein R1, R2, R3, R4, R5, and R7 are as previously disclosed, is allowed to react with trifluorotrimethylsilane in the presence of a catalytic amount of tetrabutylammonium fluoride in a polar aprotic solvent, such as tetrahydrofuran (THF), as in step b of Scheme I. The compound of Formula IV can be transformed into the compound of Formula V, wherein Y is selected from Br, Cl or I, and R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, by reaction with a halogenating reagent, such as N-bromosuccinimide and triethyl phosphite in a non-reactive solvent, such as dichloromethane (CH₂Cl₂) at reflux temperature to provide Y═Br, or such as thionyl chloride and pyridine in a hydrocarbon solvent, such as toluene at reflux temperature to provide Y═Cl, as in step c of Scheme I.

Formation of the styrene coupling partners can be accomplished as in Schemes II, III IV and V.

In Scheme II, a vinylbenzoic acid of Formula VI, wherein R11 is (C═O)OH and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, can be converted in two steps to the vinylbenzamide of Formula VIIa, wherein R11 is (C═O)N(R14)(R15), and R8, R9, R10, R12, R13, R14, R15, and X are as previously disclosed. As in step d of Scheme II, the benzoic acid of Formula VI is treated with oxalyl chloride in the presence of a catalytic amount of N,N-dimethylformamide (DMF) in a non-reactive solvent such as CH₂Cl₂ to form the acid chloride, which is subsequently allowed to react with an amine (HN(R14)(R15)), wherein R14 and R15 are as previously disclosed, in the presence of a base, such as triethylamine, in a polar aprotic solvent, such as THF, to provide the vinyl benzamide of Formula VIIa, wherein R11 is (C═O)N(R14)(R15), and R8, R9, R10, R12, R13, R14, R15, X1, X2, and X3 are as previously disclosed, as in step e of Scheme II.

In Schemes III and IV, a halobenzoic acid of Formula VIII, wherein R18 is Br or I, R11 is (C═O)OH and R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed can be converted to a vinylbenzoic acid ester of Formula VIIb1 or Formula VIIb2, wherein R18 is Br or I, R11 is (C═O)O(C₁-C₆ alkyl), and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed. In step f of Scheme III, the halobenzoic acid of Formula VIII, wherein R18 is Br, is treated with a base, such as n-butyllithium (n-BuLi), and DMF in a polar, aprotic solvent, such as THF, at a temperature of about −78° C. The resulting formyl benzoic acid is allowed to react with an acid, such as sulfuric acid (H₂SO₄), in the presence of an alcohol, such as ethyl alcohol (EtOH), as in step g, to provide the formyl benzoic acid ethyl ester of Formula IX, wherein R11 is (C═O)O(C₁-C₆ alkyl), and R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed. The vinyl benzoic acid ester of Formula VIIb1 is accessed via reaction of the compounds of Formula IX, with a base, such as potassium carbonate (K₂CO₃), and methyl triphenyl phosphonium bromide in a polar aprotic solvent, such as 1,4-dioxane, at ambient temperature, as in step h of Scheme III.

In step i of Scheme IV, the halobenzoic acid of Formula VIII, wherein R18 is Br, R11 is (C═O)OH, and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, is treated with di-tert-butyl dicarbonate in the presence of a base, such as triethylamine (Et₃N) and a catalytic amount of 4-(dimethylamino)pyridine (DMAP) in a polar aprotic solvent, such as THF, at ambient temperature. The resulting benzoic acid tert-butyl ester is allowed to react with vinyl boronic anhydride pyridine complex in the presence of a palladium catalyst, such a tetrakis(triphenylphospine)palladium(0) (Pd(PPh₃)₄), and a base, such as K₂CO₃, in a non-reactive solvent such as toluene at reflux temperature, as in step j, to provide the vinyl benzoic acid ester of Formula VIIb2, wherein R11 is (C═O)O(C₁-C₆ alkyl), and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed.

In step k of Scheme V, the vinyl benzoic acid ester of Formula VIIb2, wherein R10 is Br, R11 is (C═O)O(C₁-C₆ alkyl), and R8, R9, R12, R13, X1, X2, and X3 are as previously defined, can be further transformed into the corresponding vinyl benzoic acid ester of Formula VIIb3, wherein R10 is CN, R11 is (C═O)O(C₁-C₆ alkyl), and R8, R9, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with copper(I) cyanide (CuCN) in a polar aprotic solvent, such as DMF, at 140° C.

Coupling of the compounds of Formula V with the compounds of Formula VIIa, VIIb1, VIIb2 and VIIb3 can be accomplished as in Schemes VI, VII, and VIII. In step l of Scheme VI, a compound of Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the vinylbenzamide of Formula VIIa, wherein R11 is (C═O)N(R14)(R15), and R8, R9, R10, R12, R13, R14, R15, X1, X2, and X3 are as previously disclosed, are allowed to react in the presence of copper(I) chloride (CuCl) and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180° C. to provide the molecules of Formula One, wherein R11 is (C═O)N(R14)(R15), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, R14, R15, X1, X2, and X3 are as previously disclosed.

In step l of Scheme VII, the compound of Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the vinylbenzoic acid ester of Formula VIIb1, wherein R11 is (C═O)O(C₁-C₆ alkyl), and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180° C. to provide the compounds of Formula Xa, wherein R11 is (C═O)O(C₁-C₆ alkyl), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed. The compounds of Formula Xa are then converted to the molecules of Formula One, wherein R11 is (C═O)N(R14)(R15), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, R14, R15, X1, X2, and X3 are as previously disclosed, by either a two-step process as disclosed in steps m and n or in one step as disclosed in step o. In step m of Scheme VII, the ester of Formula Xa is saponified to the corresponding acid under acidic conditions, such as about 11 Normal (N) hydrochloric acid (HCl), in a polar aprotic solvent, such as 1,4-dioxane, at about 100° C. The acid can subsequently be coupled to an amine (HN(R14)(R15)), wherein R14 and R15 are as previously disclosed, using peptide coupling reagents, such as 1-hydroxybenzotriazole (HOBt), N-(3-dimethylaminopropyl)-N′-ethyl-carbodiimide hydrochloride (EDC.HCl), benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP), 2-chloro-1,3-dimethylimidazolidinium hexafluorophosphate (CIP), 1-hydroxy-7-azabenzotriazole (HOAt), or O-benzotriazole-N,N,N′,N′-tetramethyl-uronium-hexafluoro-phosphate (HBTU) in the presence of a base, such as N,N-diisopropylethylamine (DIEA) or 4-(dimethylamino)pyridine (DMAP), to give the molecules of Formula One, wherein R11 is (C═O)N(R14)(R15), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, R14, R15, X1, X2, and X3 are as previously disclosed. Alternatively, the ester of Formula Xa is allowed to react with an amine (HN(R14)(R15)) in the presence of a solution of trimethylaluminum in toluene in a non-reactive solvent, such as CH₂Cl₂, at ambient temperature, as in step o of Scheme VII, to access the molecules of Formula One, wherein R11 is (C═O)N(R14)(R15), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, R14, R15, X1, X2, and X3 are as previously disclosed.

In step l of Scheme VIII, the compound of Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the vinylbenzoic acid ester of Formula VIIb2 or VIIb3, wherein R11 is (C═O)O(C₁-C₆ alkyl), and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180° C. to provide the compounds of Formula Xb, wherein R11 is (C═O)OH, and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, R14, R15, X1, X2, and X3 are as previously disclosed. The compounds of Formula Xb are then converted to the molecules of Formula One, wherein R11 is (C═O)N(R14)(R15), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, R14, R15, X1, X2, and X3 are as previously disclosed, in one step as disclosed in step n. In step n of Scheme VIII, the acid of Formula Xb can be coupled to an amine (HN(R14)(R15)), wherein R14 and R15 are as previously disclosed, using peptide coupling reagents, such as 1-hydroxybenzotriazole (HOBt), N-(3-dimethylaminopropyl)-N′-ethyl-carbodiimide hydrochloride (EDC.HCl), benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP), 2-chloro-1,3-dimethylimidazolidinium hexafluorophosphate (CIP), 1-hydroxy-7-azabenzotriazole (HOAt), or O-benzotriazole-N,N,N′,N′-tetramethyl-uronium-hexafluoro-phosphate (HBTU) in the presence of a base, such as N,N-diisopropylethylamine (DIEA) or 4-(dimethylamino)pyridine (DMAP), to give the molecules of Formula One, wherein R11 is (C═O)N(R14)(R15), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, R14, R15, X1, X2, and X3 are as previously disclosed.

In step t of Scheme XIII, the vinyl benzyl chloride of Formula XIa, wherein R11 is —CH₂Cl and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously defined, can be transformed into the corresponding phthalimide-protected benzyl amine of Formula XIIa, wherein R11 is CH₂N(Phthalimide), and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with potassium phthalimide in a polar aprotic solvent, such as DMF, at 70° C.

In step u of Scheme XIV, the 4-methylbenzonitrile of Formula XIIIa, wherein R11 is CH₃ and R9, R10, R12, R13, X1, X2, and X3 are as previously defined, can be transformed into the corresponding benzyl bromide of Formula XIVa, wherein R11 is CH₂Br and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with N-bromosuccinimide (NBS) and azobisisobutyronitrile (AIBN) in a non-reactive solvent, such as carbon tetrachloride at 77° C. The nitrile group (CN) of Formula XIVa can be reduced to the corresponding aldehyde of Formula XVa, wherein R11 is CH₂Br and R9, R10, R12, R13, X1, X2, and X3 are as previously defined via reaction with diisobutylaluminum hydride (DIBAL-H) in an aprotic solvent, such as toluene, at 0° C., followed by quenching with 1.0 M hydrochloric acid (HCl) as in step v of Scheme XIV. The compound of Formula XVa can be further transformed to the corresponding phthalimide-protected benzyl amine of Formula XVIa, wherein R11 is CH₂N(Phthalimide) and R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with potassium phthalimide in a polar aprotic solvent, such as DMF, at 60° C. as in step t of Scheme XIV. In step w of Scheme XIV, the aldehyde of Formula XVIa can be converted to the olefin of Formula XIIb, wherein R11 is CH₂N(Phthalimide) and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with methyl triphenyl phosphonium bromide in a polar aprotic solvent, such as 1,4-dioxane, in the presence of a base, such as K₂CO₃, at ambient temperature.

The aldehyde of Formula XVa, wherein R11 is CH₂Br and R9, R10, R12, R13, X1, X2, and X3 are as previously defined, can be reacted with a nucleophile, such as 2-aminopyridine, in a polar aprotic solvent, such as N,N-dimethylacetamide (DMA), in the presence of a base, such as K₂CO₃, at ambient temperature to provide the compound of Formula XVII, wherein R11 is CH₂NH(2-pyridine) and R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, as in step x of Scheme XV. In step w of Scheme XV, the compound of Formula XVII can be converted to the olefin of Formula XVIII, wherein R11 is CH₂NH(2-pyridine) and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed.

In a two-step, one-pot reaction as in steps y and z of Scheme XVI, the compound of Formula XIX can be reacted with the compounds of Formula XX, wherein R10 and R11 are Cl, X1 is N, and R9, R13, X2, and X3 are as previously disclosed, in the presence of a base, such as sodium hydride (NaH), and a polar aprotic solvent, such as DMF, at ambient temperature to provide the compounds of Formula XXI, wherein R10 is Cl, R11 is (CH)NH₂CO₂CH₂CH₃, X1 is N, and R9, R13, X2, and X3 are as previously defined. Hydrolysis and decarboxylation of the compounds of Formula XXI can be accomplished by reaction under acidic conditions, such as with 3 N HCl, at reflux temperature, to afford the compounds of Formula XXII, wherein R10 is Cl, R11 is CH₂NH₂.HCl, X1 is N, and R9, R13, X2, and X3 are as previously disclosed, as in step aa in Scheme XVI. The compounds of Formula XXII can be further transformed to the corresponding phthalimide-protected benzyl amines of Formula XXIIIa, wherein R10 is Cl, R11 is CH₂N(Phthalimide), X1 is N, and R9, R13, X1, X2, and X3 are as previously disclosed, by reaction with phthalic anhydride in the presence of a base, such as Et₃N, and an aprotic solvent, such as toluene, at reflux temperature as in step ab of Scheme XVI. The bromide of Formula XXIIIa can be converted to the olefin of Formula XIIc, wherein R10 is Cl, R11 is CH₂N(Phthalimide), X1 is N, and R8, R9, R13, X2 and X3 are as previously disclosed, by reaction with vinyl boronic anhydride pyridine complex in the presence of a palladium catalyst, such as Pd(PPh₃)₄, and a base, such as K₂CO₃, in a non-reactive solvent such as toluene at reflux temperature, as in step ac of Scheme XVI.

In step u of Scheme XVII, the 4-methylnaphthonitrile of Formula XIIIb, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring, R11 is CH₃, and R12, R13, X1 and X2 are as previously defined, can be transformed into the corresponding naphthyl bromide of Formula XIVb, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring, R11 is CH₂Br, and R12, R13, X1 and X2 are as previously disclosed, by reaction with N-bromosuccinimide (NBS) and azobisisobutyronitrile (AIBN) in a non-reactive solvent, such as carbon tetrachloride at 77° C. The nitrile group (CN) of Formula XIVb can be reduced to the corresponding aldehyde of Formula XVb, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring (or if desired a non-aromatic ring), R11 is CH₂Br, and R12, R13, X1 and X2 are as previously defined via reaction with diisobutylaluminum hydride (DIBAL-H) in an aprotic solvent, such as toluene, at 0° C., followed by quenching with 1.0 M HCl as in step v of Scheme XVII. The compound of Formula XVb can be further transformed to the corresponding phthalimide-protected benzyl amine of Formula XVIb, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring, R11 is CH₂N(Phthalimide), and R12, R13, X1 and X2 are as previously disclosed, by reaction with potassium phthalimide in a polar aprotic solvent, such as DMF, at 60° C. as in step t of Scheme XVII. In step w of Scheme XVII, the aldehyde of Formula XVIb can be converted to the olefin of Formula XIId, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring, R11 is CH₂N(Phthalimide), and R8, R12, R13, X1 and X2 are as previously disclosed, by reaction with methyl triphenyl phosphonium bromide in a polar aprotic solvent, such as 1,4-dioxane, in the presence of a base, such as K₂CO₃, at ambient temperature.

The compound of Formula XXIV, wherein R11 is NHNH₂.HCl and R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, can be transformed into the corresponding phthalimide-protected hydrazine of Formula XXV, wherein R11 is NHN(Phthalimide) and R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with phthalic anhydride in glacial acetic acid at reflux temperature as in step ad of Scheme XVIII. The bromide of Formula XXV can be converted to the olefin of Formula XIIe, wherein R11 is NHN(Phthalimide) and R8, R9, R10, R13, X1, X2 and X3 are as previously disclosed, by reaction with vinyl boronic anhydride pyridine complex in the presence of a palladium catalyst, such as Pd(PPh₃)₄, and a base, such as K₂CO₃, in a polar aprotic solvent such as 1,2-dimethoxyethane at 150° C. under microwave conditions, as in step ae of Scheme XVIII.

In step af of Scheme XIX, the compound of Formula XXVI, wherein R11 is B(OH)₂, and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, are allowed to react with 2-hydroxyisoindoline-1,3-dione in the presence of CuCl and pyridine in a solvent, such as 1,2-dichlorobenzene, at ambient temperature to provide the compound of Formula XIIf, wherein R11 is ON(Phthalimide) and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed.

In step l of Scheme XX, the compound of Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds of Formula XIIa, wherein R11 is CH₂N(Phthalimide) and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180° C. to provide the corresponding compounds of Formula XXVIIa, wherein R11 is CH₂N(Phthalimide) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed. The phthalimide protecting group in the compounds of Formula XXVIIa is removed as in step ag of Scheme XX by reaction with hydrazine hydrate in a polar protic solvent such as EtOH at 90° C. to provide the compounds of Formula XXVIIIa, wherein R11 is CH₂NH₂ and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed. The compounds of Formula XXVIIIa can be transformed into the compounds of Formula One, wherein R11 is CH₂N(C═O)(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by acylation with an anhydride, such as acetic anhydride, and a base, such as Et₃N, in a non-reactive solvent such as CH₂Cl₂ at 0° C. as in step ah₁ of Scheme XX.

In step l of Scheme XXI, the compound of Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds of Formula XIIb, wherein R11 is CH₂N(Phthalimide) and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180° C. to provide the corresponding compounds of Formula XXVIIb, wherein R11 is CH₂N(Phthalimide) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed. The phthalimide protecting group in the compounds of Formula XXVIIb is removed as in step ag of Scheme XXI by reaction with hydrazine hydrate in a polar protic solvent such as EtOH at 90° C. to provide the compounds of Formula XXVIIIb, wherein R11 is CH₂NH₂ and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed. The compounds of Formula XXVIIIb can be transformed into the compounds of Formula One, wherein R11 is CH₂N(C═O)(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with an acid in the presence of HOBt.H₂O, EDC.HCl and a base, such as DIEA, in a polar aprotic solvent, such as DMF, as in step ah_(a) of Scheme XXI.

In another embodiment, the compounds of Formula XXVIIIb can be transformed into the compounds of Formula One, wherein R11 is CH₂N(C═S)(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with a thioacid in the presence of HOBt.H₂O, EDC.HCl and a base, such as DIEA, in a polar aprotic solvent, such as DMF, as in step ah₂ of Scheme XXI.

In another embodiment, the compounds of Formula XXVIIIb can be transformed into the compounds of Formula One, wherein R11 is CH₂N(C═O)N(R14)(R15) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, in two steps. The first step (step ah_(3a) of Scheme XXI) involves reaction with an aldehyde in a polar protic solvent such as methyl alcohol, followed by reaction with sodium borohydride. The second step (step ah_(3b) of Scheme XXI) involves acylation with an acid chloride, such as cyclopropylcarbonyl chloride, and a base, such as Et₃N, in a non-reactive solvent such as CH₂Cl₂ at ambient temperature of Scheme XXI.

In another embodiment, the compounds of Formula XXVIIIb can be transformed into the compounds of Formula One, wherein R11 is CH₂N(C═O)N(R14)(R15) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with an isocyanate (step ai₁ of Scheme XXI) or a carbamoyl chloride (step ai₂ of Scheme XXI) in the presence of a base such as Et₃N and in a non-reactive solvent such as CH₂Cl₂ at 0° C.

In another embodiment, the compounds of Formula XXVIIIb can be transformed into the compounds of Formula One, wherein R11 is CH₂N(C═S)N(R14)(R15) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with an isothiocyanate in the presence of a base such as Et₃N and in a non-reactive solvent such as CH₂Cl₂ at 0° C., as in steps aj of Scheme XXI.

In another embodiment, the compounds of Formula XXVIIIb can be transformed into the compounds of Formula One, wherein R11 is CH₂N(C═O)O(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with a dicarbonate, such as di-tert-butyl dicarbonate in the presence of a base such as Et₃N and in a non-reactive solvent such as CH₂Cl₂ at ambient temperature, as in steps ak of Scheme XXI.

In yet another embodiment, the compounds of Formula XXVIIIb can be transformed into the compounds of Formula One, wherein R11 is CH₂N(C═O)(C═O)O(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with a chlorooxalic acid ester, such as 2-chloro-2-oxoacetate in the presence of a base such as Et₃N and in a non-reactive solvent such as CH₂Cl₂ at 0° C., as in steps al of Scheme XXI.

In step l of Scheme XXII, the compound of Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds of Formula XIIc, wherein R10 is Cl, R11 is CH₂N(Phthalimide), X1 is N, and R8, R9, R12, R13, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180° C. to provide the corresponding compounds of Formula XXVIIc, wherein R10 is Cl, R11 is CH₂N(Phthalimide), X1 is N, and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X2, and X3 are as previously disclosed. The phthalimide protecting group in the compounds of Formula XXVIIc is removed as in step ag of Scheme XXII by reaction with hydrazine hydrate in a polar protic solvent such as EtOH at 90° C. to provide the compounds of Formula XXVIIIc, wherein R10 is Cl, R11 is CH₂NH₂, X1 is N, and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X2, and X3 are as previously disclosed. The compounds of Formula XXVIIIc can be transformed into the compounds of Formula One, wherein R10 is Cl, R11 is CH₂N(C═O)(R14), X1 is N, and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X2, and X3 are as previously disclosed, by reaction with an acid in the presence of HOBt.H₂O, EDC.HCl and a base, such as DIEA, in a polar aprotic solvent, such as CH₂Cl₂, as in step ah_(2b) of Scheme XXII.

In step l of Scheme XXIII, the compound of Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds of Formula XIId, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring (or if desired a non-aromatic ring), R11 is CH₂N(Phthalimide) and R8, R9, R12, R13, X1 and X2 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180° C. to provide the corresponding compounds of Formula XXVIId, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring, R11 is CH₂N(Phthalimide) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X1 and X2 are as previously disclosed. The phthalimide protecting group in the compounds of Formula XXVIId is removed as in step ag of Scheme XXIII by reaction with hydrazine hydrate in a polar protic solvent such as EtOH at 90° C. to provide the compounds of Formula XXVIIId, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring, R11 is CH₂NH₂ and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X1 and X2 are as previously disclosed. The compounds of Formula XXVIIId can be transformed into the compounds of Formula One, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring, R11 is CH₂N(C═O)(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X1 and X2 are as previously disclosed, by reaction with an acid in the presence of HOBt.H₂O, EDC.HCl and a base, such as DIEA, in a polar aprotic solvent, such as CH₂Cl₂, as in step ah_(2b) of Scheme XXIII

In another embodiment, the compounds of Formula XXVIIId can be transformed into the compounds of Formula One, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring, R11 is CH₂N(C═O)N(R14)(R15) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1 and X2 are as previously disclosed, by reaction with an isocyanate in the presence of a base such as Et₃N and in a non-reactive solvent such as CH₂Cl₂ at 0° C. as in step ai₁ of Scheme XXIII.

In step l of Scheme XXIV, the compound of Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds of Formula XIIe, wherein R11 is NHN(Phthalimide) and R8, R9, R12, R13, X1, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180° C. to provide the corresponding compounds of Formula XXVIIe, wherein R11 is NHN(Phthalimide) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X1, X2, and X3 are as previously disclosed. The phthalimide protecting group in the compounds of Formula XXVIIe is removed as in step ag of Scheme XXIV by reaction with hydrazine hydrate in a polar protic solvent such as EtOH at 90° C. to provide the compounds of Formula XXVIIIe, wherein R11 is NHNH₂ and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X1, X2, and X3 are as previously disclosed. The compounds of Formula XXVIIIe can be transformed into the compounds of Formula One, wherein R11 is NHN(C═O)(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with an acid in the presence of HOBt.H₂O, EDC.HCl and a base, such as DIEA, in a polar aprotic solvent, such as CH₂Cl₂, as in step ah_(2b) of Scheme XXIV.

In step l of Scheme XXV, the compound of Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds of Formula XIIf, wherein R11 is ON(Phthalimide) and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180° C. to provide the corresponding compounds of Formula XXVIIf, wherein R11 is ON(Phthalimide) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed. The phthalimide protecting group in the compounds of Formula XXVIIf is removed as in step ag of Scheme XXV by reaction with hydrazine hydrate in a polar protic solvent such as EtOH at 90° C. to provide the compounds of Formula XXVIIIf, wherein R11 is ONH₂ and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed. The compounds of Formula XXVIIIf can be transformed into the compounds of Formula One, wherein R11 is ON(C═O)(R14) and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, by reaction with an acid in the presence of HOBt.H₂O, EDC.HCl and a base, such as DIEA, in a polar aprotic solvent, such as CH₂Cl₂, as in step ah_(2b) of Scheme XXV.

In step l of Scheme XXVI, the compound of Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds of Formula XVIII, wherein R11 is CH₂NH(2-pyridine) and R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180° C. to provide the corresponding compounds of Formula One, wherein R11 is CH₂NH(2-pyridine), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, X1, X2, and X3 are as previously disclosed.

The compounds of Formula One can be further elaborated by standard methods. For example, when R11 contains a thioether, the thioether can be oxidized to the sulfone by treatment with oxone in the presence of an acetone:water mixture at ambient temperature. When R11 contains an oxalate ester, the compound of Formula One can be transformed into the corresponding oxalamide by reaction with an amine hydrochloride and a solution of trimethylaluminum in toluene in a non-reactive solvent such as CH₂Cl₂.

In Scheme XXVII, a fluorobenzaldehyde of Formula XXIX, wherein R10, X1, X2, and X3 are as previously disclosed can be converted to a (1,2,4-triazol-1-yl)benzaldehyde of Formula XXX, wherein R11 is a substituted or unsubstituted 1,2,4-triazol-1-yl group, and R10, X1, X2, and X3 are as previously disclosed by reaction with a substituted or unsubstituted 1,2,4-triazole in the presence of a base, such as potassium carbonate, in a solvent such as DMF as in step aj. In step ak, the (1,2,4-triazol-1-yl)benzaldehyde of Formula XXX is converted to a (1,2,4-triazol-1-yl)vinyl benzene of Formula XXXIa wherein R11 is a substituted or unsubstituted 1,2,4-triazol-1-yl group, and R8, R10, X1, X2, and X3 are as previously disclosed by reaction with triphenyl phosphonium bromide in the presence of a base, such as potassium carbonate, in an aprotic solvent, such as 1,4-dioxane.

In Scheme XXVIII, a bromofluorobenzene of Formula XXXII, wherein R10, X1, X2, and X3 are as previously disclosed can be converted to a (1,2,4-triazol-1-yl)vinylbenzene of Formula XXXIb, wherein R11 is a substituted or unsubstituted 1,2,4-triazol-1-yl group, and R8, R10, X1, X2, and X3 are as previously disclosed in two steps. In step al, the bromofluorobenzene is reacted with a substituted or unsubstituted 1,2,4-triazole in the presence of a base, such as potassium carbonate, in a solvent such as DMF to generate the (1,2,4-triazol-1-yl)bromobenzene. In step cl, the (1,2,4-triazol-1-yl)bromobenzene is reacted with vinyl boronic anhydride pyridine complex in the presence of a catalyst, such as Pd (PPh₃)₄, and a base, such as potassium carbonate in a solvent such as toluene.

Coupling of the compounds of Formula V with compounds of Formula XXXIa and XXXIb can be accomplished as in Schemes XXIX. In step l, a compound of Formula V, wherein Y is Br, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and a vinylbenzene of Formula XXXIa or XXXIb, wherein R11 is a substituted or unsubstituted 1,2,4-triazol-1-yl group, and R8, R9, R10, X1, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180° C. to provide the molecules of Formula One, wherein R11 is a substituted or unsubstituted 1,2,4-triazol-1-yl group, and R1, R2, R3, R4, R5, R6, R7, R8, R10, X1, X2, and X3 are as previously disclosed.

In Scheme XXX, compounds of Formula XXXIII wherein R11 is a 3-nitro-1,2,4-triazol-1-yl group, and R1, R2, R3, R4, R5, R6, R7, R8, R10, X1, X2, and X3 are as previously disclosed can be converted to compounds of Formula One, wherein R11 is a 3-amido-1,2,4-triazol-1-yl group, and R1, R2, R3, R4, R5, R6, R7, R8, R10, X1, X2, and X3 are as previously disclosed by a two-step process. In step am, the 3-nitro-1,2,4-triazol-1-yl group is reduced to a 3-amino-1,2,4-triazol-1-yl group in the presence of zinc dust and ammonium chloride in a protic solvent, such as methanol. In step an, the 3-amino-1,2,4-triazol-1-yl group is acylated with an acid chloride, such as cyclopropylcarbonyl chloride or acetyl chloride, in the presence of a base, such as triethylamine, in a solvent such as dichloromethane.

In step ao of Scheme XXXI, a bromophenyl methyl ketone of Formula XXXIV wherein R10, X1, X2, and X3 are as previously disclosed is converted to an phenyl methyl ketone of the Formula XXXV wherein R11 is a 1,2,4-triazol-1-yl group, and R10, X1, X2, and X3 are as previously disclosed by treatment with 1,2,4-triazole in the presence of a base, such as cesium carbonate, and a catalyst, such as copper iodide, in a solvent, such as DMF. In step ap, the 1,2,4-triazolylacetophenone of Formula XXXV is converted to the trimethylsilyl enol ether of Formula XXXVI by treatment with trimethylsilyl triflluoromethanesulfonate in the presence of a base, such as triethylamine, in an aprotic solvent, such as dichloromethane. In step aq, the silyl enol ether is reacted with a compound of Formula V, wherein Y is Br, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene at a temperature of about 180° C. to generate a ketone of the Formula XXXVII, wherein R11 is a 1,2,4-triazol-1-yl group, and R1, R2, R3, R4, R5, R6, R7, R10, X1, X2, and X3 are as previously disclosed. In step ar, the ketone of the Formula XXXVII is treated with methylmagnesium bromide in an aprotic solvent, such as THF to generate the tertiary alcohol. The tertiary alcohol then undergoes an elimination reaction when treated with a catalytic amount of p-toluenesulfonic acid in a solvent, such as toluene, when heated to a temperature to allow azeotropic removal of water to produce compounds of Formula One wherein R11 is a 1,2,4-triazol-1-yl group, R8 is methyl, and R1, R2, R3, R4, R5, R6, R7, R10, X1, X2, and X3 are as previously disclosed, as in step as.

In Scheme XXXIII, a compound of Formula XXXIX, wherein X1, X2, and X3 are as previously disclosed is converted to a molecule of Formula XL, wherein X1, X2, and X3 are as previously disclosed, by treatment with a reducing agent, such as sodium cyanoborohydride, in a solvent, such as acetic acid, as in step au. In step av, the nitrogen atom is protected with a tert-butyloxycarbonyl (BOC) group by reaction with di-tert-butyl dicarbonate in the presence of a catalyst, such as DMAP, in a solvent, such as acetonitrile. The bromide of Formula XL can be converted to the olefin of Formula XLI, wherein R8, X1, X2 and X3 are as previously disclosed, by reaction with potassium vinyl trifluoroborate in the presence of a palladium catalyst, such as PdCl₂(dppf), and a base, such as K₂CO₃, in a polar aprotic solvent such as DMSO at 100° C., as in step aw.

In Scheme XXXIV, a compound of Formula XXXIX, wherein X1, X2, and X3 are as previously disclosed is converted to a molecule of Formula XLII, wherein X1, X2, and X3 are as previously disclosed in two steps. In step ax, the olefin is formed by treatment of the bromide with potassium vinyl trifluoroborate in the presence of a palladium catalyst, such as PdCl₂, and a ligand, such as triphenylphosphine, and a base, such as Cs₂CO₃, in a solvent mixture such as THF/H₂O. In step ay, the nitrogen atom is protected with a tert-butyloxycarbonyl (BOC) group by reaction with di-tert-butyl dicarbonate in the presence of a catalyst, such as DMAP, in a solvent, such as acetonitrile.

In step l of Scheme XXXV, the compound of Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds of Formula XLI or XLII, wherein R8, X1, X2 and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 150° C. to provide the corresponding compounds of Formula XLIIIa or XLIIIb, wherein R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed.

In Scheme XXXVI, a compound of Formula XLIIIa, wherein R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed is converted to a molecule of Formula XLIV, wherein R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed by treatment with trifluoroacetic acid, in a solvent such as dichloromethane, as in step az. Compounds of the Formula XLIV can then be transformed into compounds of the Formula XLV wherein R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed, in two steps. In step ba, the indoline is treated with sodium nitrite (NaNO₂), in an acid, such as concentrated HCl, at a temperature around 5° C., to form the nitrosoindole. In step bb, the nitrosoindole is reacted with ammonium chloride in the presence of zinc powder in a protic solvent, such as methanol. In step bc, compounds of the Formula XLV are transformed into compounds of the Formula XLVI, wherein X4 is N(R14)(C(═O)R14) and R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed, by treatment with and acid, such as 3,3,3-trifluoropropanoic acid, PyBOP, and a base, such as DIEA, in a polar aprotic solvent, such as dichloromethane.

In Scheme XXXVII, a compound of Formula XLIIIb, wherein R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed is converted to an indole of Formula XLVII, wherein R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed by treatment with trifluoroacetic acid, in a solvent such as dichloromethane, as in step bd. Compounds of the Formula XLVII can be transformed into compounds of the Formula XLVIII wherein R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed, by reaction with 4-nitrophenyl-2-((tert-butoxycarbonyl)amino)acetate in the presence of potassium fluoride and a crown ether, such as 18-crown-6-ether, in a solvent, such as acetonitrile, as in step be. Compounds of the Formula XLVIII can be transformed into compounds of the Formula XLIX, wherein R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed in two steps. In step bf, the Boc group is removed by treatment with trifluoroacetic acid, in a solvent such as dichloromethane. In step bg, the amine is treated with 3,3,3-trifluoropropanoic acid, PyBOP, and a base, such as DIEA, in a polar aprotic solvent, such as dichloromethane.

In Scheme XXXVIII, a compound of Formula L, wherein X1, X2, and X3 are as previously disclosed is converted to a compound of the Formula LI, wherein X1, X2, and X3 are as previously disclosed by treatment with copper (II) sulfate pentahydrate and Zn powder in a base, such as sodium hydroxide as in step bh. Compounds of the Formula LI can be transformed into compounds of the Formula LII wherein X1, X2, and X3 are as previously disclosed, by reaction with hydrazine, in a solvent such as water, at a temperature around 95° C., as in step bi. In step bj, the olefin of the Formula LIII wherein X1, X2, and X3 are as previously disclosed is formed by treatment of the bromide with potassium vinyl trifluoroborate in the presence of a palladium catalyst, such as PdCl₂(dppf), and a base, such as K₂CO₃, in a solvent mixture such as DMSO. Compounds of the Formula LIV, wherein X1, X2, and X3 are as previously disclosed, can be formed from compounds of the Formula LIII by reaction with ethyl bromoacetate, in the presence of a base, such as Cs₂CO₃, in a solvent, such as DMF.

In step l of Scheme XXXIX, the compound of Formula V, wherein Y, R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compound of Formula LIV, wherein R8, X1, X2 and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180° C. to provide the corresponding compound of Formula LV, wherein R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed. The compound of Formula LV can be further transformed into a compound of the Formula LVI, wherein R1, R2, R3, R4, R5, R6, R7, R8, X1, X2, and X3 are as previously disclosed, in two steps. In step bl, the ester is hydrolyzed to the acid in the presence of HCl and acetic acid, at a temperature of about 100° C. In step bm, the acid is treated with an amine, such as 2,2,2-trifluoroethylamine, PyBOP, and a base, such as DIEA, in a polar aprotic solvent, such as dichloromethane.

In step bn of Scheme XL, carboxylic acids of the Formula LVII, wherein R11 is C(═O)OH and R8, R10, X1, X2, and X3 are as previously disclosed and compounds of the Formula V, wherein Y is Br and R1, R2, R3, R4, R5, R6, and R7 are as previously disclosed are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as N-methyl pyrrolidine, at a temperature of about 150° C. to afford compounds of Formula LVIII, wherein R11 is (C═O)OH and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, X1, X2, and X3 are as previously disclosed. Compounds of the Formula LVIII can be further transformed to the corresponding benzamides of Formula LIX, wherein R11 is (C═O)N(R14)(R15), and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, X1, X2, and X3 are as previously disclosed, by treatment with an amine, such as 2-amino-N-(2,2,2-trifluoroethyl)acetamide, PyBOP, and a base, such as DIEA, in a polar aprotic solvent, such as dichloromethane, as in step bo.

EXAMPLES

The examples are for illustration purposes and are not to be construed as limiting the invention disclosed in this document to only the embodiments disclosed in these examples.

Starting materials, reagents, and solvents that were obtained from commercial sources were used without further purification. Anhydrous solvents were purchased as Sure/Seal™ from Aldrich and were used as received. Melting points were obtained on a Thomas Hoover Unimelt capillary melting point apparatus or an OptiMelt Automated Melting Point System from Stanford Research Systems and are uncorrected. Molecules are given their known names, named according to naming programs within ISIS Draw, ChemDraw, or ACD Name Pro. If such programs are unable to name a molecule, the molecule is named using conventional naming rules. ¹H NMR spectral data are in ppm (δ) and were recorded at 300, 400, or 600 MHz, and ¹³C NMR spectral data are in ppm (δ) and were recorded at 75, 100, or 150 MHz, unless otherwise stated.

Example 1: Preparation of 1-(1-Bromo-2,2,2-trifluoroethyl)-3,5-dichlorobenzene (AI1)

Step 1 Method A. 1-(3,5-Dichlorophenyl)-2,2,2-trifluoroethanol (AI2)

To a stirred solution of 1-(3,5-dichlorophenyl)-2,2,2-trifluoroethanone (procured from Rieke Metals, UK; 5.0 grams (g), 20.5 millimoles (mmol)) in methyl alcohol (CH₃OH; 100 milliliters (mL)) at 0° C. were added sodium borohydride (NaBH₄; 3.33 g, 92.5 mL) and 1 Normal (N) aqueous sodium hydroxide solution (NaOH; 10 mL). The reaction mixture was warmed to 25° C. and stirred for 2 hours (h). After the reaction was deemed complete by thin layer chromatography (TLC), saturated (satd) aqueous (aq) ammonium chloride (NH₄Cl) solution was added to the reaction mixture, and the mixture was concentrated under reduced pressure. The residue was diluted with diethyl ether (Et₂O) and washed with water (H₂O; 3×50 mL). The organic layer was dried over sodium sulfate (Na₂SO₄) and concentrated under reduced pressure to afford the title compound as a liquid (4.0 g, 79%): ¹H NMR (400 MHz, CDCl₃) δ 7.41 (m, 3H), 5.00 (m, 2H), 2.74 (s, 1H); ESIMS m/z 242.97 ([M−H]⁻).

Step 1 Method B. 1-(3,5-Dichlorophenyl)-2,2,2-trifluoroethanol (AI2)

To a stirred solution of 3,5-dichlorobenzaldehyde (10 g, 57 mmol) in tetrahydrofuran (THF; 250 mL) were added trifluoromethyltrimethylsilane (9.79 g, 69.2 mmol) and a catalytic amount of tetrabutylammonium fluoride (TBAF). The reaction mixture was stirred at 25° C. for 8 h. After the reaction was deemed complete by TLC, the reaction mixture was diluted with 3 N hydrochloric acid (HCl) and then was stirred for 16 h. The reaction mixture was diluted with H₂O and was extracted with ethyl acetate (EtOAc; 3×). The combined organic extracts were washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure to afford the title compound as a liquid (8.41 g, 60%).

The following compounds were made in accordance with the procedures disclosed in Step 1 Method A of Example 1 above.

2,6-Difluoro-4-(2,2,2-trifluoro-1-hydroxyethyl)benzonitrile

The product was isolated as a brown solid: mp 83-87° C.; ¹H NMR (300 MHz, CDCl₃) δ 7.26 (d, J=9.0 Hz, 2H), 5.12 (d, J=6.0 Hz, 1H), 3.06 (s, 1H); ESIMS m/z 237.1 ([M+H]⁺).

The following compounds were made in accordance with the procedures disclosed in Step 1 Method B of Example 1 above.

2,2,2-Trifluoro-1-(3,4,5-trichlorophenyl)ethanol (AI3)

The product was isolated as a pale yellow liquid (500 mg, 65%): ¹H NMR (400 MHz, CDCl₃) δ 7.45 (s, 2H), 5.00 (m, 1H), 2.80 (s, 1H); ESIMS m/z 278 ([M+H]⁺); IR (thin film) 3420, 1133, 718 cm⁻¹.

1-(3,5-Dichloro-4-fluorophenyl)-2,2,2-trifluoroethanol (AI4)

The product was isolated as a pale yellow liquid (500 mg, 65%): ¹H NMR (400 MHz, CDCl₃) δ 7.41 (s, 2H), 5.00 (m, 1H), 2.80 (s, 1H); ESIMS m/z 262 ([M+H]⁺); IR (thin film) 3420, 1133, 718 cm⁻¹.

1-(3,4-Dichlorophenyl)-2,2,2-trifluoroethanol (AI5)

The product was isolated as a pale yellow liquid (500 mg, 65%): ¹H NMR (400 MHz, CDCl₃) δ 7.60 (s, 1H), 7.51 (m, 1H), 7.35 (m, 1H), 5.01 (m, 1H), 2.60 (s, 1H); EIMS m/z 244 ([M]⁺).

1-(3,5-Dibromophenyl)-2,2,2-trifluoroethanol

The title molecule was isolated as a colorless liquid: ¹H NMR (300 MHz, CDCl₃) δ 7.67 (s, 1H), 7.58 (s, 2H), 5.08-5.02 (m, 1H), 4.42 (bs, 1H); EIMS m/z 333.7 ([M]⁺); IR (thin film) 3417, 2966, 1128, 531 cm⁻¹.

2,2,2-Trifluoro-1-(3-fluoro-5-(trifluoromethyl)phenyl)ethanol

The title molecule was isolated as a clear, colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 7.56 (s, 1H), 7.45-7.37 (m, 2H), 5.11 (q, J=6.4 Hz, 1H), 3.22 (bs, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 162.42 (d, J=249.5 Hz), 137.46 (d, J=7.8 Hz), 132.89 (qd, J=33.5, 7.9 Hz), 123.67 (q, J=283.8 Hz), 122.92 (q, J=270.68 Hz), 120.10 (t, J=4.1 Hz), 118.13 (d, J=23.0 Hz), 113.94 (dq, J=24.2, 3.9 Hz), 71.57 (q, J=32.4 Hz); EIMS m/z 262 ([M]⁺).

1-(3-Chloro-5-(trifluoromethyl)phenyl)-2,2,2-trifluoroethanol

The product was isolated as a white solid (4.98 g, 77%): mp 42-46° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.83-7.50 (m, 3H), 5.10 (p, J=6.2 Hz, 1H), 2.88 (d, J=4.3 Hz, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 137.12, 135.84, 131.4, 133.03 (q, J=33.3 Hz), 127.15 (q, J=3.8 Hz), 124.50 (q, J=308.0 Hz), 123.45 (q, J=301.8 Hz), 123.04, 72.06 (q, J=32.5 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −62.93, −78.43; EIMS m/z 278 ([M]⁺).

2,2,2-Trifluoro-1-(4-fluoro-3-(trifluoromethyl)phenyl)ethanol

The product was isolated as a brown liquid: ¹H NMR (400 MHz, CDCl₃) δ 7.76 (d, J=6.8 Hz, 1H), 7.69-7.67 (m, 1H), 7.28-7.23 (m, 1H), 5.05-5.02 (m, 1H); ESIMS m/z 261.1 ([M−H]⁻); IR (thin film) 3418, 1131 cm⁻¹.

2,2,2-Trifluoro-1-(3,4,5-trifluorophenyl)ethanol

The product was isolated as a colorless liquid: ¹H NMR (300 MHz, CDCl₃) δ 7.19-7.10 (m, 2H), 5.03-4.96 (m, 1H), 2.85 (bs, 1H); EIMS m/z 230.1 ([M]⁺).

2,2,2-Trifluoro-1-(2,3,4-trifluorophenyl)ethanol

The product was isolated as a clear colorless liquid (4.61 g 66%): ¹H NMR (400 MHz, CDCl₃) δ 7.23 (qd, J=7.4, 6.1, 4.2 Hz, 1H), 6.93 (tdd, J=9.2, 6.9, 2.2 Hz, 1H), 5.25 (q, J=6.3 Hz, 1H), 3.02-2.74 (m, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 151.79 (ddd, J=254.5, 9.8, 3.4 Hz), 149.52 (ddd, J=253.5, 11.0, 3.5 Hz), 139.67 (dt, J=252.5, 15.3 Hz), 123.68 (q, J=282.2 Hz), 122.48 (dt, J=8.2, 4.1 Hz), 118.95 (dd, J=10.6, 3.6 Hz), 112.73 (dd, J=17.7, 3.9 Hz), 66.58-64.42 (m); ¹⁹F NMR (376 MHz, CDCl₃) δ −78.95 (d, J=6.2 Hz), −132.02 (dd, J=20.0, 8.2 Hz), −137.89 (m), 159.84 (t, J=20.3 Hz); EIMS m/z 230 ([M]⁺).

2,2,2-Trifluoro-1-(2,4,5-trichlorophenyl)ethanol

The product was isolated as a white solid (3.37 g, 73%): mp 70-73° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.63 (d, J=2.5 Hz, 1H), 7.54 (d, J=2.5 Hz, 1H), 5.72-5.57 (m, 1H), 2.85 (d, J=4.8 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −77.84.

1-(4-Chloro-3-nitrophenyl)-2,2,2-trifluoroethanol

The product was isolated as a yellow oil (6.52 g, 73%): ¹H NMR (400 MHz, CDCl₃) δ 8.04 (d, J=2.0 Hz, 1H), 7.75-7.51 (m, 2H), 5.16 (m, 1H), 3.41 (d, J=4.3 Hz, 1H); ¹³C NMR (101 MHz, CDCl3) δ 147.65, 134.44, 132.23, 132.17, 128.11, 124.66, 123.60 (q, J=283.8), 70.99 (q, J=32.6 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −78.47; EIMS m/z 230 ([M]⁺).

2,2,2-Trifluoro-1-(4-fluoro-3,5-dimethylphenyl)ethanol

The product was isolated as a white solid (6.49 g, 84%): mp 45-49° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.10 (d, J=6.8 Hz, 2H), 4.89 (m, 1H), 2.63 (d, J=4.3 Hz, 1H), 2.27 (d, J=2.2 Hz, 6H); ¹³C NMR (101 MHz, CDCl₃) δ 160.45 (d, J=246.0 Hz), 128.73, 127.97, 124.92 (d, J=18.6 Hz), 124.19 (q, J=279.1 Hz), 72.36 (q, J=32.0 Hz), 14.61 (d, J=4.1 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −78.48, −120.14; EIMS m/z 222 ([M]⁺).

2,2,2-Trifluoro-1-(4-fluoro-3-methylphenyl)ethanol

The product was isolated as a white solid (2.12 g, 33%): mp 40-46° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.28 (d, J=7.4 Hz, 1H), 7.25-7.14 (m, 1H), 7.01 (t, J=8.9 Hz, 1H), 5.05-4.63 (m, 1H), 3.03 (d, J=4.2 Hz, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 161.91 (d, J=247.0 Hz), 130.62 (d, J=5.6 Hz), 129.41 (d, J=3.5 Hz), 126.55 (d, J=8.5 Hz), 115.19 (d, J=22.9 Hz), 72.23 (q, J=32.1 Hz), 14.44 (d, J=3.6 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −78.57, −116.15; EIMS m/z 208 ([M]⁺).

1-(3-Chloro-4-methylphenyl)-2,2,2-trifluoroethanol

The product was isolated as a clear colorless oil (4.99 g, 75%): ¹H NMR (400 MHz, CDCl3) δ 7.31 (s, 1H), 7.10 (m, 2H), 4.79 (q, J=6.1 Hz, 1H), 2.89 (bs, 1H), 2.25 (s, 3H); ¹³C NMR (101 MHz, CDCl3) δ 137.64, 134.67, 132.99, 131.09, 128.01, 125.58, 124.02 (q, J=284.8 Hz), 72.08 (q, J=32.3 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −78.39; EIMS m/z 224.5 ([M]⁺).

1-(3,4-Dibromophenyl)-2,2,2-trifluoroethanol

The product was isolated as a clear colorless oil (5.92 g, 88%): ¹H NMR (400 MHz, CDCl₃) δ 7.76 (d, J=2.0 Hz, 1H), 7.66 (d, J=8.3 Hz, 1H), 7.29 (dd, J=8.3, 2.0 Hz, 1H), 4.99 (qd, J=6.4, 4.2 Hz, 1H), 2.75 (d, J=4.3 Hz, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 134.52, 133.81, 132.60, 127.45, 126.19, 125.16, 123.71 (q, J=283.8 Hz), 71.57 (q, J=32.5 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −78.44; EIMS m/z 334 ([M]⁺).

2,2,2-Trifluoro-1-(3-(trifluoromethoxy)phenyl)ethanol

The product was isolated as a clear colorless oil (20.9 g, 79%): ¹H NMR (400 MHz, CDCl₃) δ 7.55-7.36 (m, 3H), 7.33-7.14 (m, 1H), 5.06 (m, 1H), 2.80 (br m, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 149.36 (q, J=2.0 Hz), 136.04, 129.99, 125.78, 123.91 (q, J=282.8 Hz), 121.90, 120.31 (q, J=258.6 Hz), 120.12, 72.04 (q, J=32.3 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −57.92, −78.49; EIMS m/z 260 ([M]⁺).

2-Fluoro-5-(2,2,2-trifluoro-1-hydroxyethyl)benzonitrile

The product was isolated as a clear colorless oil (5.47 g, 58%): ¹H NMR (400 MHz, CDCl₃) δ 7.80 (dd, J=5.9, 2.2 Hz, 1H), 7.76 (ddd, J=7.8, 5.0, 2.3 Hz, 1H), 7.30 (d, J=8.6 Hz, 1H), δ 5.09 (qd, J=6.3, 4.2 Hz, 1H), 3.12 (br m, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 163.49 (d, J=261.7 Hz), 134.23 (d, J=8.6 Hz), 132.67, 131.17, 123.66 (q, J=282.4 Hz), 116.79 (d, J=20.1 Hz), 113.39, 100.96 (d, J=194.9), 71.07 (q, J=32.5 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −78.70, −105.22; EIMS m/z 219 ([M]⁺).

1-(3-Bromo-5-chlorophenyl)-2,2,2-trifluoroethanol

The product was isolated as a yellow liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 7.78 (s, 1H), 7.67 (s, 1H), 7.57 (s, 1H), 7.15 (d, J=5.7 Hz, 1H); EIMS m/z 288 ([M]⁺); IR (thin film) 3435, 1175, 750 cm⁻¹.

1-(3-Bromo-5-fluorophenyl)-2,2,2-trifluoroethanol

The product was isolated as a pale yellow liquid: ¹H NMR (400 MHz, CDCl₃) δ 7.43 (s, 1H), 7.29-7.26 (m, 1H), 7.18 (d, J=8.8 Hz, 1H), 5.03-4.98 (m, 1H), 3.60 (bs, 1H). EIMS m/z 272.0 ([M]⁺); IR (thin film) 3400, 1176, 520 cm⁻¹.

1-(3,5-Dichlorophenyl)-2,2,3,3,3-pentafluoropropan-1-ol

Using pentafluoroethyltrimethylsilane, the product was isolated as a white solid (6.22 g, 88%): mp 71-73° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.42 (t, J=1.9 Hz, 1H), 7.37 (d, J=1.8 Hz, 2H), 5.11 (dt, J=16.2, 5.7 Hz, 1H), 2.62 (d, J=4.9 Hz, 1H); ¹³C NMR (101 MHz, CDCl₃) δ 136.90, 135.31, 129.84, 126.38, 70.94 (dd, J=28.2, 23.1 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −81.06, −120.94 (d, J=277.5 Hz), −129.18 (d, J=277.5 Hz); EIMS m/z 295 ([M]⁺).

2,2,3,3,3-Pentafluoro-1-(3,4,5-trichlorophenyl)propan-1-ol

Using pentafluoroethyltrimethylsilane, the product was isolated as an off white semi solid: ¹H NMR (300 MHz, DMSO-d₆) δ 7.78 (s, 2H), 7.29 (d, J=5.4 Hz,), 5.50-5.40 (m, 1H); EIMS m/z 328.0 ([M]⁺); IR (thin film) 3459, 1188, 797 cm⁻¹.

2,2,2-Trifluoro-1-(3-(trifluoromethyl)phenyl)ethanol

The product was isolated as a light yellow oil (13.8, 89%): ¹H NMR (400 MHz, CDCl₃) δ 7.77 (s, 1H), 7.70-7.67 (m, 2H), 7.55 (t, J=7.8 Hz, 1H), 5.12 (q, J=6.6 Hz, 1H), 2.76 (s, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −62.8, −78.5; EIMS m/z 244 ([M]⁺).

Step 2. 1-(1-Bromo-2,2,2-trifluoroethyl)-3,5-dichlorobenzene (AI1)

To a stirred solution of 1-(3,5-dichlorophenyl)-2,2,2-trifluoroethanol (4.0 g, 16.3 mmol) in dichloromethane (CH₂Cl₂; 50 mL), were added N-bromosuccinimide (NBS; 2.9 g, 16.3 mmol) and triphenyl phosphite (5.06 g, 16.3 mmol), and the resultant reaction mixture was heated at reflux for 18 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to 25° C. and was concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 100-200 mesh; eluting with 100% pentane) afforded the title compound as a liquid (2.0 g, 40%): ¹H NMR (400 MHz, CDCl₃) δ 7.41 (s, 3H), 5.00 (m, 1H); EIMS m/z 306 ([M]⁺).

The following compounds were made in accordance with the procedures disclosed in Step 2 of Example 1.

5-(1-Bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (AI6)

The product was isolated as a colorless oil (300 mg, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.59 (s, 2H), 5.00 (m, 1H); EIMS m/z 340.00 ([M]⁺).

5-(1-Bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-fluorobenzene (AI7)

The product was isolated as a colorless oil (320 mg, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.45 (s, 2H), 5.00 (m, 2H); EIMS m/z 324.00 ([M]⁺).

4-(1-Bromo-2,2,2-trifluoroethyl)-1,2-dichlorobenzene (AI8)

The product was isolated as a colorless oil (300 mg, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.63 (s, 1H), 7.51 (m, 1H), 7.35 (m, 1H), 5.01 (m, 1H); EIMS m/z 306.00 ([M]⁺).

1,3-Dibromo-5-(1-bromo-2,2,2-trifluoroethyl)benzene

The title molecule was isolated as a colorless liquid: ¹H NMR (300 MHz, CDCl₃) δ 7.71 (s, 1H), 7.59 (s, 2H), 5.04-4.97 (m, 1H); EIMS m/z 394.6 ([M]⁺); IR (thin film) 1114, 535 cm⁻¹.

1-(1-Bromo-2,2,2-trifluoroethyl)-3-fluoro-5-(trifluoromethyl)benzene

The title molecule was isolated as a colorless liquid: ¹H NMR (400 MHz, DMSO-d₆) δ 7.90 (d, J=8.4 Hz, 1H), 7.79-7.77 (m, 2H), 6.40-6.34 (m, 1H); EIMS m/z 324.00 ([M]⁺); IR (thin film) 1175, 525 cm⁻¹.

1-(1-Bromo-2,2,2-trifluoroethyl)-3-chloro-5-(trifluoromethyl)benzene

The title molecule was isolated as a colorless liquid: ¹H NMR (400 MHz, CDCl3) δ 7.71 (s, 1H), 7.67 (s, 1H), 7.64 (s, 1H), 5.15-5.09 (m, 1H); EIMS m/z 340.00 ([M]⁺); IR (thin film) 1178, 750, 540 cm⁻¹.

4-(1-Bromo-2,2,2-trifluoroethyl)-1-fluoro-2-(trifluoromethyl)benzene

The title molecule was isolated as a colorless liquid: ¹H NMR (400 MHz, CDCl₃) δ 7.75-7.72 (m, 2H), 7.28-7.24 (m, 1H), 5.19-5.16 (m, 1H); EIMS m/z 326.0 ([M]⁺); IR (thin film) 1114, 571 cm⁻¹.

5-(1-Bromo-2,2,2-trifluoroethyl)-1,2,3-trifluorobenzene

The title molecule was isolated as a brown liquid: ¹H NMR (300 MHz, CDCl₃) δ 7.23-7.12 (m, 2H), 5.05-4.98 (m, 1H); EIMS m/z 292.0 ([M]⁺); IR (thin film) 1116, 505 cm⁻¹.

1-(1-Bromo-2,2,2-trifluoroethyl)-2,3,4-trifluorobenzene

The title molecule was isolated as a colorless oil: ¹H NMR (300 MHz, CDCl₃) δ 7.44 (m, 1H), 7.11-7.03 (m, 1H), 5.53-5.45 (m, 1H).

1-(1-Bromo-2,2,2-trifluoroethyl)-2,4,5-trichlorobenzene

The title molecule was isolated as an off white solid: ¹H NMR (300 MHz, DMSO-d₆) δ 8.06 (d, J=2.1 Hz, 1H), 7.71 (s, 1H), 6.45-6.37 (m, 1H); EIMS m/z 340.0 ([M]⁺); IR (thin film) 1186, 764, 576 cm⁻¹.

4-(1-Bromo-2,2,2-trifluoroethyl)-1-chloro-2-nitrobenzene

The title molecule was isolated as an off white solid: ¹H NMR (300 MHz, DMSO-d₆) δ 8.30 (s, 1H), 7.92 (d, J=9.0 Hz, 1H), 6.43-6.35 (m, 1H); EIMS m/z 317.0 ([M]⁺); IR (thin film) 2927, 1540, 1353, 1177, 766, 530 cm⁻¹.

5-(1-Bromo-2,2,2-trifluoroethyl)-2-fluoro-1,3-dimethylbenzene

The title molecule was isolated as a colorless liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 7.32 (d, J=7.2 Hz, 2H), 6.15-6.07 (m, 1H), 3.23 (s, 6H); ESIMS m/z 284.1 ([M+H]⁺); IR (thin film) 2962, 1112, 500 cm⁻¹.

4-(1-Bromo-2,2,2-trifluoroethyl)-1-fluoro-2-methylbenzene

The title molecule was isolated as a colorless liquid: ¹H NMR (300 MHz, CDCl₃) δ 7.34-7.28 (m, 2H), 7.04-6.98 (m, 1H), 5.10-5.03 (m, 1H), 2.29 (s, 3H); EIMS m/z 270.1 ([M]⁺); IR (thin film) 2989, 1163 cm⁻¹.

1-(1-Bromo-2,2,3,3,3-pentafluoropropyl)-3,5-dichlorobenzene

The title molecule was isolated as a colorless liquid: ¹H NMR (400 MHz, DMSO-d₆) δ 7.79 (t, J=2.0 Hz, 1H), 7.63 (s, 2H), 6.37-6.29 (m, 1H); EIMS m/z 356([M]⁺); IR (thin film) 1673, 1130, 715, 518 cm⁻¹.

4-(1-Bromo-2,2,2-trifluoroethyl)-2-chloro-1-methylbenzene

The title molecule was isolated as a liquid: ¹H NMR (300 MHz, CDCl₃) δ 7.55-7.50 (m, 2H), 7.44 (d, J=8.4 Hz, 1H), 6.24-6.16 (m, 1H); IR (thin film) 2983, 1112, 749, 564 cm⁻¹.

1,2-Dibromo-4-(1-bromo-2,2,2-trifluoroethyl)benzene

The title molecule was isolated as a colorless liquid: ¹H NMR (300 MHz, CDCl₃) δ 7.75 (s, 1H), 7.67 (d, J=8.4 Hz, 1H), 7.33-7.30 (m, 1H), 5.07-5.00 (m, 1H); EIMS m/z 393.8 ([M]⁺); IR (thin film) 2981, 1644, 1165 cm⁻¹.

1-(1-Bromo-2,2,2-trifluoroethyl)-3-(trifluoromethoxy)benzene

The title molecule was isolated as a colorless liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 7.65-7.60 (m, 2H), 7.56-7.50 (m, 2H), 6.35-6.27 (m, 1H); EIMS m/z 322 ([M]⁺); IR (thin film) 3413, 1161, 564 cm⁻¹.

5-(1-Bromo-2,2,2-trifluoroethyl)-2-fluorobenzonitrile

The title molecule was isolated as a pale yellow liquid: ¹H NMR (300 MHz, CDCl₃) δ 8.15-8.12 (m, 1H), 8.00-7.98 (m, 1H), 7.69-7.63 (m, 1H), 6.31-6.26 (m, 1H); EIMS m/z 280.9 ([M]⁺).

1-Bromo-3-(1-bromo-2,2,2-trifluoroethyl)-5-chlorobenzene

The title molecule was isolated as a pale yellow liquid: ¹H NMR (400 MHz, DMSO-d₆) δ 7.90 (s, 1H), 7.74 (s, 1H), 7.65 (s, 1H), 6.26-6.20 (m, 1H); EIMS m/z 349.9 ([M]⁺); IR (thin film) 1114, 764 cm⁻¹.

1-Bromo-3-(1-bromo-2,2,2-trifluoroethyl)-5-fluorobenzene

The title molecule was isolated as a colorless liquid: ¹H NMR (400 MHz, CDCl₃) δ 7.43 (s, 1H), 7.32-7.29 (m, 1H), 7.22 (d, J=8.8 Hz, 1H), 1.06 (q, 1H); EIMS m/z 334.0 ([M]⁺); IR (thin film) 3087, 1168, 533 cm⁻¹.

5-(1-Bromo-2,2,3,3,3-pentafluoropropyl)-1,2,3-trichlorobenzene

The title molecule was isolated as a colorless liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 7.85 (s, 2H), 6.38-6.29 (m, 1H); EIMS m/z 389.9 ([M]⁺); IR (thin film) 1208, 798, 560 cm⁻¹.

4-(1-Bromo-2,2,2-trifluoroethyl)-2,6-difluorobenzonitrile

The title molecule was isolated as a purple solid: mp 59-63° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.25 (s, 2H), 5.11-5.07 (m, 1H); ESIMS m/z 299.0 ([M+H]⁺).

1-(1-Bromo-2,2,2-trifluoroethyl)-3-(trifluoromethyl)benzene

The title molecule was isolated as a colorless liquid: mp 59-63° C.; ¹H NMR (300 MHz, CDCl3) δ 7.75-7.67 (m, 3H), 7.57-7.52 (m, 1H), 5.20-5.13 (m, 1H); ESIMS m/z 306.0 ([M]⁺); IR (thin film) 3436, 2925, 1265, 749 cm⁻¹.

Example 2: Preparation of N-Methyl-4-vinylbenzamide (AI9)

Step 1. 4-Vinylbenzoyl chloride (AI10)

To a stirred solution of 4-vinylbenzoic acid (1 g, 6.75 mmol) in CH₂Cl₂ (20 mL) at 0° C. were added a catalytic amount of N,N-dimethylformamide (DMF) and oxalyl chloride (1.27 g, 10.12 mmol) dropwise over a period of 15 minutes (min) The reaction mixture was stirred at 25° C. for 6 h. After the reaction was deemed complete by TLC, the reaction mixture was concentrated under reduced pressure to give the crude acid chloride.

Step 2. N-Methyl-4-vinylbenzamide (AI9)

To 1 M N-methylamine in THF (13.5 mL, 13.5 mmol) at 0° C. were added triethylamine (Et₃N; 1.34 mL, 10.12 mmol) and the acid chloride from Step 1 above in THF (10 mL), and the reaction mixture was stirred at 25° C. for 3 h. After the reaction was deemed complete by TLC, the reaction mixture was quenched with water and then was extracted with EtOAc (3×). The combined EtOAc layer was washed with brine and dried over Na₂SO₄ and concentrated under reduced pressure to afford the title compound as an off-white solid (650 mg, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.76 (d, J=8.0 Hz, 2H), 7.45 (d, J=8.0 Hz, 2H), 6.79 (m, 1H), 6.20 (br s, 1H), 5.82 (d, J=17.6 Hz, 1H), 5.39 (d, J=10.8 Hz, 1H); ESIMS m/z 161.95 ([M+H]⁺).

The following compounds were made in accordance with the procedures disclosed in accordance with Example 2.

N,N-Dimethyl-4-vinylbenzamide (AI11)

The product was isolated as an off-white solid (650 mg, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.42 (m, 4H), 6.71 (m, 1H), 5.80 (d, J=17.6 Hz, 1H), 5.31 (d, J=10.8 Hz, 1H), 3.05 (s, 3H), 3.00 (s, 3H); ESIMS m/z 176.01 ([M+H]⁺).

N-(2,2,3-Trifluoromethyl)-4-vinylbenzamide (AI12)

The product was isolated as an off-white solid (900 mg, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.76 (d, J=8.0 Hz, 2H), 7.45 (d, J=8.0 Hz, 2H), 6.79 (m, 1H), 6.20 (br s, 1H), 5.82 (d, J=17.6 Hz, 1H), 5.39 (d, J=10.8 Hz, 1H), 4.19 (m, 2H); ESIMS m/z 230.06 ([M+H]⁺).

Morpholino(4-vinylphenyl)methanone (AI13)

The product was isolated as a white solid (850 mg, 60%): ESIMS m/z 218.12 ([M+H]⁺).

Example 3: Preparation of Ethyl 2-methyl-4-vinylbenzoate (AI14)

Step 1. 4-Formyl-2-methylbenzoic acid (AI15)

To a stirred solution of 4-bromo-2-methylbenzoic acid (10 g, 46.4 mmol) in dry THF (360 mL) at −78° C. was added n-butyllithium (n-BuLi, 1.6 M solution in hexane; 58.17 mL, 93.0 mmol) and DMF (8 mL). The reaction mixture was stirred at −78° C. for 1 h then was warmed to 25° C. and stirred for 1 h. The reaction mixture was quenched with 1 N HCl solution and extracted with EtOAc. The combined EtOAc extracts were washed with brine and dried over Na₂SO₄ and concentrated under reduced pressure. The residue was washed with n-hexane to afford the title compound as a solid (3.0 g, 40%): mp 196-198° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 13.32 (br s, 1H), 10.05 (s, 1H), 7.98 (m, 1H), 7.84 (m, 2H), 2.61 (s, 3H); ESIMS m/z 163.00 ([M−H]⁻).

Step 2. Ethyl 4-formyl-2-methylbenzoate (AI16)

To a stirred solution of 4-formyl-2-methylbenzoic acid (3 g, 18.2 mmol) in ethyl alcohol (EtOH; 30 mL) was added sulfuric acid (H₂SO₄, x M; 2 mL), and the reaction mixture was heated at 80° C. for 18 h. The reaction mixture was cooled to 25° C. and concentrated under reduced pressure. The residue was diluted with EtOAc and washed with H₂O. The combined EtOAc extracts were washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure to afford the title compound as a solid (2.8 g, 80%): ¹H NMR (400 MHz, CDCl₃) δ 10.05 (s, 1H), 8.04 (m, 1H), 7.75 (m, 2H), 4.43 (m, 2H), 2.65 (s, 3H), 1.42 (m, 3H).

Step 3. Ethyl 2-methyl-4-vinylbenzoate (AI14)

To a stirred solution of ethyl 4-formyl-2-methylbenzoate (2.8 g, 4 mmol) in 1,4-dioxane (20 mL) were added potassium carbonate (K₂CO₃; 3.01 g, 21.87 mmol) and methyltriphenyl phosphonium bromide (7.8 g, 21.87 mmol) at 25° C. Then the reaction mixture was heated at 100° C. for 18 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to 25° C. and filtered, and the filtrate was concentrated under reduced pressure. The crude compound was purified by flash chromatography (SiO₂, 100-200 mesh; eluting with 25-30% EtOAc in n-Hexane) to afford the title compound as a solid (2.0 g, 72%): ¹H NMR (400 MHz, CDCl₃) δ 7.86 (m, 1H), 7.27 (m, 2H), 6.68 (dd, J=17.6, 10.8 Hz, 1H), 5.84 (d, J=17.6 Hz, 1H), 5.39 (d, J=10.8 Hz, 1H), 4.39 (m, 2H), 2.60 (s, 3H), 1.40 (m, 3H); ESIMS m/z 191.10 ([M−H]⁻); IR (thin film) 2980, 1716, 1257 cm⁻¹.

Example 4: Preparation of tert-Butyl 2-chloro-4-vinylbenzoate (AI17)

Step 1. tert-Butyl 4-bromo-2-chlorobenzoate (AI18)

To a stirred solution of 4-bromo-2-chlorobenzoic acid (5 g, 21.37 mmol) in THF (30 mL) was added di-tert-butyl dicarbonate (25.5 g, 25.58 mmol), Et₃N (3.2 g, 31.98 mmol) and 4-(dimethylamino)pyridine (DMAP; 0.78 g, 6.398 mmol), and the reaction mixture was stirred at 25° C. for 18 h. The reaction mixture was diluted with EtOAc and washed with H₂O. The combined organic layer was washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure. The residue was purified by flash chromatography (SiO₂, 100-200 mesh; eluting with 2-3% EtOAc in n-hexane) to afford the title compound as a liquid (3.2 g, 51%): ¹H NMR (400 MHz, CDCl₃) δ 7.62 (m, 2H), 7.44 (d, J=8.4 Hz, 1H), 1.59 (s, 9H); ESIMS m/z 290.10 ([M+H]⁺); IR (thin film) 1728 cm⁻¹.

The following compounds were made in accordance with the procedures disclosed in Step 1 of Example 4.

tert-Butyl 2-bromo-4-iodobenzoate (AI19)

The product was isolated as a colorless oil (1.2 g, 50%): ¹H NMR (400 MHz, CDCl₃) δ 8.01 (s, 1H), 7.68 (d, J=8.4 Hz, 1H), 7.41 (d, J=8.0 Hz, 1H), 1.59 (s, 9H); ESIMS m/z 382.10 ([M+H]⁺); IR (thin film) 1727 cm⁻¹.

tert-Butyl 4-bromo-2-(trifluoromethyl)benzoate (AI20)

The product was isolated as a colorless oil (1 g, 52%): ¹H NMR (400 MHz, CDCl₃) δ 7.85 (s, 1H), 7.73 (d, J=8.4 Hz, 1H), 7.62 (d, J=8.4 Hz, 1H), 1.57 (s, 9H); ESIMS m/z 324.10 ([M+H]⁺); IR (thin film) 1725 cm⁻¹.

Step 2. tert-Butyl 2-chloro-4-vinylbenzoate (AI17)

To a stirred solution of tert-butyl 4-bromo-2-chlorobenzoate (1.6 g, 5.50 mmol) in toluene (20 mL) was added tetrakis(triphenylphospine)palladium(0) (Pd(PPh₃)₄; (0.31 mg, 0.27 mmol), K₂CO₃ (2.27 g, 16.5 mmol) and vinylboronic anhydride pyridine complex (2.0 g, 8.3 mmol) and the reaction mixture was heated to reflux for 16 h. The reaction mixture was filtered, and the filtrate was washed with H₂O and brine, dried over Na₂SO₄ and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 100-200 mesh; eluting with 5-6% EtOAc in n-hexane) afforded the title compound as a liquid (0.6 g, 46%): ¹H NMR (400 MHz, CDCl₃) δ 7.72 (d, J=8.1 Hz, 1H), 7.44 (m, 1H), 7.31 (d, J=8.0 Hz, 1H), 6.69 (dd, J=17.6, 10.8 Hz, 1H), 5.85 (d, J=17.6 Hz, 1H), 5.40 (d, J=10.8 Hz, 1H), 1.60 (s, 9H); ESIMS m/z 238.95 ([M+H]⁺); IR (thin film) 2931, 1725, 1134 cm⁻¹.

The following compounds were made in accordance with the procedures disclosed in Step 2 of Example 4.

tert-Butyl 2-bromo-4-vinylbenzoate (AI21)

The product was isolated as a colorless oil (1 g, 52%): ¹H NMR (400 MHz, CDCl₃) δ 7.68 (m, 2H), 7.36 (d, J=8.0 Hz, 1H), 6.68 (dd, J=17.6, 10.8 Hz, 1H), 5.84 (d, J=17.6 Hz, 1H), 5.39 (d, J=10.8 Hz, 1H), 1.60 (s, 9H); ESIMS m/z 282.10 ([M+H]⁺); IR (thin film) 2978, 1724, 1130 cm⁻¹.

tert-Butyl 2-(trifluoromethyl)-4-vinylbenzoate (AI22)

The product was isolated as a colorless oil (1.2 g, 50%): ¹H NMR (400 MHz, CDCl₃) δ 7.71 (d, J=6.4 Hz, 2H), 7.59 (d, J=7.6 Hz, 1H), 6.77 (dd, J=17.6, 10.8 Hz, 1H), 5.89 (d, J=17.6 Hz, 1H), 5.44 (d, J=10.8 Hz, 1H), 1.58 (s, 9H); ESIMS m/z 272.20 ([M+H]⁺); IR (thin film) 2982, 1727, 1159 cm⁻¹.

Example 5: Preparation of tert-Butyl 2-cyano-4-vinylbenzoate (AI23)

To a stirred solution of tert-butyl 2-bromo-4-vinylbenzoate (0.5 g, 1.77 mmol) in DMF (20 mL) was added copper(I) cyanide (CuCN; 0.23 g, 2.65 mmol), and the reaction mixture was heated at 140° C. for 3 h. The reaction mixture was cooled to 25° C., diluted with H₂O, and extracted with EtOAc. The combined organic layer was washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure. The residue was purified by flash chromatography (SiO₂, 100-200 mesh; eluting with 15% EtOAc in n-hexane) to afford the title compound as a white solid (0.3 g, 72%): mp 51-53° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.03 (s, 1H), 7.77 (s, 1H), 7.64 (d, J=8.4 Hz, 1H), 6.75 (dd, J=17.6, 10.8 Hz, 1H), 5.93 (d, J=17.6 Hz, 1H), 5.51 (d, J=10.8 Hz, 1H), 1.65 (s, 9H); ESIMS m/z 229.84 ([M+H]⁺); IR (thin film) 2370, 1709, 1142 cm⁻¹.

Example 6: Preparation of Ethyl 2-bromo-4-iodobenzoate (AI46)

To a stirred solution of 4-iodo-2-bromobenzoic acid (5 g, 15.29 mmol) in ethyl alcohol (EtOH; 100 mL) was added sulfuric acid (H₂SO₄; 5 mL), and the reaction mixture was heated at 80° C. for 18 h. The reaction mixture was cooled to 25° C. and concentrated under reduced pressure. The residue was diluted with EtOAc (2×100 mL) and washed with H₂O (100 mL). The combined EtOAc extracts were washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure to afford the compound as a pale yellow solid (5 g, 92%): ¹H NMR (400 MHz, DMSO-d₆) δ 8.04 (d, J=1.2 Hz, 1H), 7.71 (d, J=7.6 Hz, 1H), 7.51 (d, J=8.4 Hz, 1H), 4.41 (q, J=7.2 Hz, 2H), 1.41 (t, J=7.2 Hz, 3H).

The following compounds were made in accordance with the procedures disclosed in Example 6.

Ethyl 4-bromo-2-chlorobenzoate (AI47)

The title compound was isolated as an off-white solid (2.0 g, 80%): ¹H NMR (400 MHz, DMSO-d₆) δ 8.25 (d, J=1.2 Hz, 1H), 7.79 (d, J=7.6 Hz, 1H), 7.65 (d, J=8.4 Hz, 1H), 4.65 (q, J=7.2 Hz, 2H), 1.56 (t, J=7.2 Hz, 3H).

Ethyl 4-bromo-2-methylbenzoate (AI48)

The title compound was isolated as a pale yellow liquid (3.0 g, 83%): ¹H NMR (400 MHz, CDCl₃) δ 7.79 (d, J=8.4 Hz, 1H), 7.41 (s, 1H), 7.39 (d, J=8.4 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 2.60 (s, 3H), 1.40 (t, J=7.2 Hz, 3H) ESIMS m/z 229.11 ([M+H]⁺); IR (thin film) 1725 cm⁻¹.

Ethyl 4-bromo-2-fluorolbenzoate (AI49)

The title compound was isolated as a colorless liquid (9.0 g, 79%): ¹H NMR (400 MHz, DMSO-d₆) δ 7.84 (t, J=8.4 Hz, 1H), 7.76 (d, J=2.0 Hz, 1H), 7.58 (d, J=1.6 Hz, 1H), 4.34 (q, J=7.2 Hz, 2H), 1.32 (t, J=7.2 Hz, 3H); ESIMS m/z 246.99 ([M+H]⁺), IR (thin film) 1734 cm⁻¹.

Example 7: Preparation of Ethyl 4-bromo-2-ethylbenzoate (AI50)

To a stirred solution of 4-bromo-2-fluorobenzoic acid (2.0 g, 9.17 mmol) in THF (16 mL), was added 1.0 M ethyl magnesium bromide in THF (32 mL, 32.0 mmol) dropwise at 0° C. and the resultant reaction mixture was stirred at RT for 18 h. The reaction mixture was quenched with 2 N HCl and extracted with ethyl acetate. The combined ethyl acetate layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford crude 4-bromo-2-ethylbenzoic acid as a colorless liquid that was used in the next step without purification (0.4 g): ¹H NMR (400 MHz, CDCl₃) δ 7.64 (d, J=8.4 Hz, 1H), 7.47 (m, 1H), 7.43 (m, 1H), 2.95 (q, J=4.0 Hz, 2H), 1.32 (t, J=4.0 Hz, 3H); ESIMS m/z 228.97 ([M+H]⁺).

The title compound was synthesized from 4-bromo-2-ethylbenzoic acid in accordance to the procedure in Example 6, isolated as a colorless liquid (0.15 g, 68%): ¹H NMR (400 MHz, DMSO-d₆) δ 7.90 (d, J=8.4 Hz, 1H), 7.47 (m, 2H), 4.40 (q, J=7.2 Hz, 2H), 3.06 (q, J=7.6 Hz, 2H), 1.42 (t, J=7.2 Hz, 3H), 1.26 (t, J=7.6 Hz, 3H); ESIMS m/z 226.96 ([M−H]⁻); IR (thin film) 3443, 1686, 568 cm⁻¹.

Example 8: Preparation of Ethyl 2-bromo-4-vinylbenzoate (AI51)

To a stirred solution of ethyl 2-bromo-4-iodobenzoate (5 g, 14.3 mmol) in THF/water (100 mL, 9:1) was added potassium vinyltrifluoroborate (1.89 g, 14.3 mmol), Cs₂CO₃ (18.27 g, 56.07 mmol) and triphenylphosphine (0.22 g, 0.85 mmol) and the reaction mixture was degassed with argon for 20 min, then charged with PdCl₂ (0.05 g, 0.28 mmol). The reaction mixture was heated to reflux for 16 h. The reaction mixture was cooled to RT and filtered through a celite bed and washed with ethyl acetate. The filtrate was again extracted with ethyl acetate and the combined organic layers washed with water and brine, dried over Na₂SO₄ and concentrated under reduced pressure to afford crude compound. The crude compound was purified by column chromatography (SiO₂, 100-200 mesh; eluting with 2% ethyl acetate/petroleum ether) to afford the title compound as a light brown gummy material (2 g, 56%): ¹H NMR (400 MHz, CDCl₃) δ 7.78 (d, J=8.4 Hz, 1H), 7.71 (d, J=1.2 Hz, 1H), 7.51 (d, J=8.4 Hz, 1H), 6.69 (dd, J=17.6, 10.8 Hz, 1H), 5.86 (d, J=17.6 Hz, 1H), 5.42 (d, J=11.2 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 1.43 (t, J=3.6 Hz, 3H); ESIMS m/z 255.18 ([M+H]⁺); IR (thin film) 1729 cm⁻¹.

The following compounds were made in accordance with the procedures disclosed in Example 8.

Ethyl 2-methyl-4-vinylbenzoate (AI52)

The title compound was isolated as a colorless liquid (0.8 g, 80%): ¹H NMR (400 MHz, CDCl₃) δ 7.89 (d, J=8.4 Hz, 1H), 7.27 (m, 2H), 6.79 (dd, J=17.6, 10.8 Hz, 1H), 5.86 (d, J=17.6 Hz, 1H), 5.42 (d, J=11.2 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 2.60 (s, 3H), 1.43 (t, J=7.2 Hz, 3H); ESIMS m/z 191.10 ([M+H]⁺); IR (thin film) 1717, 1257 cm⁻¹.

Ethyl 2-fluoro-4-vinylbenzoate (AI53)

The title compound was isolated as a pale yellow liquid (2.0 g, 50%): ¹H NMR (400 MHz, DMSO-d₆) δ 7.87 (t, J=8.0 Hz, 1H), 7.51 (d, J=16.0 Hz, 1H), 7.48 (d, J=16.0 Hz, 1H), 6.82 (dd, J=17.6, 10.8 Hz, 1H), 6.09 (d, J=17.6 Hz, 1H), 5.50 (d, J=10.8 Hz, 1H), 4.35 (q, J=7.2 Hz, 2H), 1.35 (t, J=7.2 Hz, 3H); ESIMS m/z 195.19 ([M+H]⁺); IR (thin film) 1728 cm⁻¹.

Example 9: Preparation of Ethyl 2-chloro-4-vinylbenzoate (AI54)

To a stirred solution of ethyl 2-chloro-4-bromobenzoate (2 g, 7.63 mmol) in dimethylsulfoxide (20 mL) was added potassium vinyltrifluoroborate (3.06 g, 22.9 mmol) and potassium carbonate (3.16 g, 22.9 mmol). The reaction mixture was degassed with argon for 30 min. Bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride (0.27 g, 0.38 mmol) was added and the reaction mixture was heated to 80° C. for 1 h. The reaction mixture was diluted with water (100 mL), extracted with ethyl acetate (2×50 mL), washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure to obtain the compound as brown gummy material (1.1 g, 69%): ¹H NMR (400 MHz, CDCl₃) δ 7.81 (d, J=8.4 Hz, 1H), 7.46 (s, 1H), 7.33 (d, J=8.4 Hz, 1H), 6.70 (dd, J=17.6, 11.2 Hz, 1H), 5.87 (d, J=17.6 Hz, 1H), 5.42 (d, J=10.8 Hz, 1H), 4.41 (q, J=7.2 Hz, 2H), 1.43 (t, J=7.2 Hz, 3H); ESIMS m/z 211.22 ([M+H]⁺); IR (thin film) 1729, 886 cm⁻¹.

The following compounds were made in accordance with the procedures disclosed in Example 9.

Ethyl 2-ethyl-4-vinylbenzoate (AI55)

The title compound was isolated as a color less liquid (1.0 g, 66%): ¹H NMR (300 MHz, CDCl₃) δ 7.85 (m, 1H), 7.29 (m, 2H), 6.76 (d, J=10.8 Hz, 1H), 5.86 (d, J=17.6 Hz, 1H), 5.36 (d, J=10.5 Hz, 1H), 4.41 (q, J=7.2 Hz, 2H), 3.10 (q, J=7.2 Hz, 2H), 1.40 (t, J=7.2 Hz, 3H), 1.30 (t, J=7.2 Hz, 3H); ESIMS m/z 205.26 ([M+H]⁺); IR (thin film) 1720, 1607, 1263 cm⁻¹.

Methyl 2-methoxy-4-vinylbenzoate (AI56)

The title compound was isolated as a pale yellow liquid (1.2 g, 75%): ¹H NMR (400 MHz, CDCl₃) δ 7.79 (d, J=8.0 Hz, 1H), 7.04 (d, J=1.2 Hz, 1H), 6.97 (s, 1H), 6.74 (dd, J=11.2, 11.2 Hz, 1H), 5.86 (d, J=17.6 Hz, 1H), 5.39 (d, J=17.6 Hz, 1H) 3.93 (s, 3H), 3.91 (s, 3H). ESIMS m/z 193.18 ([M+H]⁺); IR (thin film) 1732 cm⁻¹.

Ethyl 2-(methylthio)-4-vinylbenzoate

The title compound was isolated as a brown liquid: ¹H NMR (300 MHz, CDCl₃) δ 7.98 (d, J=8.4 Hz, 1H), 7.23-7.18 (m, 2H), 6.78 (dd, J=17.7, 10.8, Hz, 1H), 5.89 (d, J=17.4 Hz, 1H), 5.42 (d, J=10.8 Hz, 1H), 4.39-4.36 (m, 2H), 2.48 (s, 3H), 1.39 (t, J=6.9 Hz, 3H); ESIMS m/z 221.9 ([M+H]⁺); IR (thin film) 1708 cm⁻¹.

Example 10: Preparation of (E)-Ethyl 4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoate (AI24)

To a stirred solution of ethyl 2-methyl-4-vinylbenzoate (2.0 g, 10.5 mmol) in 1,2-dichlorobenzene (25 mL) were added 1-(1-bromo-2,2,2-trifluoroethyl)-3,5-dichlorobenzene (6.44 g, 21.0 mmol), copper(I) chloride (CuCl; 208 mg, 21 mmol) and 2,2bipyridyl (0.65 g, 4.1 mmol). The reaction mixture was degassed with argon for 30 min and then stirred at 180° C. for 24 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to 25° C. and filtered, and the filtrate was concentrated under reduced pressure. Purification by flash chromatography (SiO₂, 100-200 mesh; eluting with 25-30% EtOAc in petroleum ether) afforded the title compound as a solid (1.7 g, 40%): ¹H NMR (400 MHz, CDCl₃) δ 7.91 (d, J=8.0 Hz, 1H), 7.37 (m, 1H), 7.27-7.24 (m, 4H), 6.59 (d, J=16.0 Hz, 1H), 6.59 (dd, J=16.0, 8.0 Hz, 1H), 4.38 (q, J=7.2 Hz, 2H), 4.08 (m, 1H), 2.62 (s, 3H), 1.42 (t, J=7.2 Hz, 3H); ESIMS m/z 415.06 ([M−H]⁻); IR (thin film) 1717, 1255, 1114 cm⁻¹.

Compounds AI25, AI57-AI68 and AC1-AC5 (Table 1) were made in accordance with the procedures disclosed in Example 10.

(E)-Ethyl 4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)-benzoic acid (AI25)

The product was isolated as a pale brown gummy liquid (500 mg, 40%): ¹H NMR (400 MHz, CDCl₃) δ 7.79 (d, J=8.0 Hz, 1H), 7.71 (m, 1H), 7.61 (d, J=7.6 Hz, 1H), 7.42 (s, 2H), 6.70 (d, J=16.0 Hz, 1H), 6.57 (dd, J=16.0, 8.0 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 4.19 (m, 1H), 1.40 (t, J=7.6 Hz, 3H); ESIMS m/z 502.99 ([M+H]⁻); IR (thin film) 1730, 1201, 1120, 749 cm⁻¹.

(E)-Ethyl 4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-fluorobenzoate (AI57)

¹H NMR (400 MHz, CDCl₃) δ 7.38 (s, 1H), 7.26 (s, 3H), 7.21 (d, J=8.4 Hz, 1H), 7.16 (d, J=11.6 Hz, 1H), 6.59 (d, J=16.0 Hz, 1H), 6.47 (dd, J=, 16.0, 8.0 Hz, 1H), 4.41 (q, J=6.8 Hz, 2H), 4.18 (m, 1H), 1.41 (t, J=6.8 Hz, 3H); ESIMS m/z 419.33 ([M−H]⁻); IR (thin film) 1723, 1115, 802 cm⁻¹.

(E)-Ethyl 4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-bromobenzoate (AI58)

¹H NMR (400 MHz, CDCl₃) δ 7.79 (d, J=8.0 Hz, 1H), 7.67 (s, 1H), 7.38 (m, 2H), 7.26 (m, 2H), 6.56 (d, J=16.0 Hz, 1H), 6.45 (dd, J=16.0, 7.6 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 4.39 (m, 1H), 1.42 (t, J=7.2 Hz, 3H); ESIMS m/z 481.22 ([M−H]⁻); IR (thin film) 1727, 1114, 801, 685 cm⁻¹.

(E)-Ethyl 2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl) but-1-enyl)benzoate (AI59)

¹H NMR (400 MHz, CDCl₃) δ 7.79 (d, J=8.0 Hz, 1H), 7.67 (d, J=1.6 Hz, 1H), 7.40 (s, 2H), 7.36 (d, J=1.6 Hz, 1H), 6.56 (d, J=16.0 Hz, 1H), 6.44 (dd, J=16.0, 7.6 Hz, 1H), 4.42 (q, J=6.8 Hz, 2H), 4.15 (m, 1H), 1.42 (t, J=6.8 Hz, 3H); ESIMS m/z 514.74 ([M−H]⁻); IR (thin film) 1726, 1115, 808, 620 cm⁻¹.

(E)-Ethyl 2-methyl-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl) but-1-enyl)benzoate (AI60)

The title compound was isolated as a light brown gummy material: ¹H NMR (400 MHz, CDCl₃) δ 7.90 (d, J=8.8 Hz, 1H), 7.34 (d, J=6.0 Hz, 2H), 7.25 (d, J=7.2 Hz, 2H), 6.59 (d, J=16.0 Hz, 1H), 6.42 (dd, J=16.0, 8.0 Hz, 1H), 4.38 (q, J=7.2 Hz, 2H), 4.19 (m, 1H), 2.63 (s, 3H), 1.41 (t, J=7.2 Hz, 3H).

(E)-Ethyl 2-chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl) but-1-enyl)benzoate (AI61)

¹H NMR (400 MHz, CDCl₃) δ 7.87 (d, J=8.0 Hz, 1H), 7.46 (d, J=1.6 Hz, 1H), 7.40 (s, 2H), 7.31 (d, J=1.6 Hz, 1H), 6.57 (d, J=16.0 Hz, 1H), 6.44 (dd, J=16.0 Hz, 8.0 Hz, 1H), 4.42 (q, J=6.8 Hz, 2H), 4.15 (m, 1H), 1.42 (t, J=6.8 Hz, 3H); ESIMS m/z 470.73 ([M−H]⁻); IR (thin film) 1726, 1115, 809, 3072 cm⁻¹.

(E)-Ethyl 4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)benzoate (AI62)

The title compound was isolated as a pale brown liquid (1.0 g, 46.3%): ¹H NMR (400 MHz, CDCl₃) δ 7.79 (d, J=8.0 Hz, 1H), 7.71 (s, 1H), 7.61 (d, J=7.6 Hz, 1H), 7.41 (s, 2H) 6.65 (d, J=16.0 Hz, 1H), 6.49 (dd, J=16.0, 8.0 Hz, 1H), 4.42 (q, J=7.6 Hz, 2H), 4.15 (m, 1H), 1.42 (t, J=7.6 Hz, 3H); ESIMS m/z 502.99 ([M−H]⁻); IR (thin film) 1730, 1202, 1120, 750 cm⁻¹.

(E)-Ethyl 2-chloro-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoate (AI63)

¹H NMR (400 MHz, CDCl₃) δ 7.85 (d, J=6.0 Hz, 1H), 7.46 (d, J=1.8 Hz, 2H), 7.34 (m, 1H), 7.24 (m, 1H), 6.57 (d, J=16.2 Hz, 1H), 6.45 (dd, J=16.2, 7.2 Hz, 1H), 4.43 (q, J=7.2 Hz, 2H), 4.13 (m, 1H), 1.41 (t, J=7.2 Hz, 3H); ESIMS m/z 455.0 ([M+H]⁺); IR (thin film) 1728, 1115, 817 cm⁻¹.

(E)-Ethyl 2-fluoro-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoate (AI64)

¹H NMR (400 MHz, CDCl₃) δ 7.93 (t, J=7.6 Hz, 1H), 7.34 (d, J=5.6 Hz, 2H), 7.21 (d, J=8.0 Hz, 1H), 7.16 (d, J=11.6 Hz, 1H), 6.59 (d, J=16.0 Hz, 1H), 6.49 (dd, J=16.0, 7.6 Hz, 1H), 4.42 (q, J=7.6 Hz, 2H), 4.13 (m, 1H), 1.41 (t, J=7.6 Hz, 3H); ESIMS m/z 436.81 ([M−H]⁻); IR (thin film) 1725 cm⁻¹.

(E)-Ethyl 2-bromo-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoate (AI65)

¹H NMR (400 MHz, CDCl₃) δ 7.94 (d, J=8.0 Hz, 1H), 7.67 (s, 1H), 7.36 (m, 3H), 6.56 (d, J=15.6 Hz, 1H), 6.44 (dd, J=15.6, 8.0 Hz, 1H), 4.42 (q, J=6.8 Hz, 2H), 4.10 (m, 1H), 1.42 (t, J=6.8 Hz, 3H); ESIMS m/z 498.74 ([M−H]⁻); IR (thin film) 1726, 1114, 820, 623 cm⁻¹.

(E)-Ethyl 2-methyl-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoate (AI66)

The title compound was isolated as a brown semi-solid: ¹H NMR (400 MHz, CDCl₃) δ 7.90 (d, J=8.8 Hz, 1H), 7.34 (d, J=6.0 Hz, 2H), 7.25 (d, J=7.2 Hz, 2H), 6.59 (d, J=16.0 Hz, 1H), 6.42 (dd, J=16.0 Hz, 8.0 Hz, 1H), 4.38 (q, J=7.2 Hz, 2H), 4.19 (m, 1H), 2.63 (s, 3H), 1.41 (t, J=7.2 Hz, 3H); ESIMS m/z 432.90 ([M−H]⁻); IR (thin film) 1715 cm⁻¹.

(E)-Methyl 2-methoxy-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoate (AI67)

¹H NMR (400 MHz, CDCl₃) δ 7.80 (d, J=8.4 Hz, 1H), 7.35 (d, J=6.0 Hz, 2H), 7.03 (d, J=1.2 Hz, 1H), 6.92 (s, 1H), 6.59 (d, J=15.6 Hz, 1H), 6.42 (dd, J=15.6, 8.0 Hz, 1H), 4.13 (m, 1H), 3.93 (s, 3H), 3.88 (s, 3H); ESIMS m/z 437.29 ([M+H]⁺); IR (thin film) 1724 cm⁻¹.

(E)-Ethyl 2-ethyl-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoate (AI68)

¹H NMR (400 MHz, CDCl₃) δ 7.85 (d, J=8.0 Hz, 1H), 7.35 (d, J=9.6 Hz, 2H), 7.26 (m, 1H), 7.24 (m, 1H), 6.60 (d, J=15.6 Hz, 1H), 6.42 (dd, J=15.6, 8.0 Hz, 1H), 4.38 (q, J=7.2 Hz, 2H), 4.14 (m, 1H), 3.01 (q, J=7.6 Hz 2H), 1.41 (t, J=7.2 Hz, 3H), 1.26 (t, J=7.6 Hz, 3H); ESIMS m/z 447.05 ([M−H]⁻); IR (thin film) 1715, 1115, 817 cm⁻¹.

(E)-Ethyl 4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(methylthio)benzoate

Isolated as a brown liquid: ¹H NMR (400 MHz, CDCl₃) δ 7.99 (d, J=8.1 Hz, 2H), 7.35-7.32 (m, 2H), 7.21-7.16 (m, 2H), 6.63 (d, J=15.8 Hz, 1H), 6.45 (dd, J=15.9, 7.8 Hz, 1H), 4.41-4.31 (m, 2H), 4.30-4.10 (m, 1H), 2.47 (s, 3H), 1.40 (t, J=7.5 Hz, 3H); ESIMS m/z 466.88 ([M+H]⁺); IR (thin film) 1705, 1114 cm⁻¹.

Example 11: Preparation of (E)-4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoic acid (AI32)

To a stirred solution of (E)-ethyl 4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoate (1.7 g, 4.0 mmol) in 1,4-dioxane (10 mL) was added 11 N HCl (30 mL), and the reaction mixture was heated at 100° C. for 48 h. The reaction mixture was cooled to 25° C. and concentrated under reduced pressure. The residue was diluted with H₂O and extracted with chloroform (CHCl₃). The combined organic layer was dried over Na₂SO₄ and concentrated under reduced pressure, and the crude compound was washed with n-hexane to afford the title compound as a white solid (0.7 g, 50%): mp 142-143° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 12.62 (br s, 1H), 7.81 (d, J=8.0 Hz, 1H), 7.66 (s, 3H), 7.52-7.44 (m, 2H), 6.89 (dd, J=16.0, 8.0 Hz, 1H), 6.78-6.74 (d, J=16.0 Hz, 1H), 4.84 (m, 1H), 2.50 (s, 3H); ESIMS m/z 387.05 ([M−H]⁻); IR (thin film) 3448, 1701, 1109, 777 cm⁻¹.

The following compounds were made in accordance with the procedures disclosed in Example 11.

(E)-2-Methyl-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic acid (AI26)

The product was isolated as a pale brown gummy liquid (1 g, 46%): ¹H NMR (400 MHz, CDCl₃) δ 7.97 (d, J=8.0 Hz, 1H), 7.77 (s, 1H), 7.65 (m, 1H), 7.41 (s, 2H), 6.68 (d, J=16.0 Hz, 1H), 6.53 (dd, J=16.0, 8.0 Hz, 1H), 4.16 (m, 1H), 2.50 (s, 3H); ESIMS m/z 422.67 ([M−H]⁻).

(E)-2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic acid (AI27)

The product was isolated as an off-white semi-solid (1 g, 45%): ¹H NMR (400 MHz, CDCl₃) δ 7.99 (d, J=8.4 Hz, 1H), 7.50 (m, 1H), 7.40 (s, 1H), 7.36 (m, 2H), 6.59 (d, J=15.6 Hz, 1H), 6.48 (dd, J=15.6, 7.6 Hz, 1H), 4.14 (m, 1H); ESIMS m/z 442.72 ([M−H]⁻); IR (thin film) 3472, 1704, 1113, 808 cm⁻¹.

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic acid (AI28)

The product was isolated as a brown solid (1 g, 45%): mp 70-71° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.99 (d, J=8.0 Hz, 1H), 7.72 (s, 1H), 7.40 (m, 3H), 6.58 (d, J=16.0 Hz, 1H), 6.48 (dd, J=16.0, 8.0 Hz, 1H), 4.14 (m, 1H); ESIMS m/z 484.75 ([M−H]⁻); IR (thin film) 3468, 1700 cm⁻¹.

(E)-2-Cyano-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic acid (AI29)

The product was isolated as an off-white solid (500 mg, 45%): mp 100-101° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.90 (s, 1H), 7.85 (d, J=7.6 Hz, 1H), 7.72 (d, J=8.0 Hz, 1H), 7.65 (br s, 1H), 7.42 (s, 2H), 6.73 (d, J=16.0 Hz, 1H), 6.58 (dd, J=16.0, 8.0 Hz, 1H), 4.19 (m, 1H); ESIMS m/z 431.93 ([M−H]⁻).

(E)-4-(3-(3,4-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoic acid (AI30)

The product was isolated as a pale brown liquid (500 mg, 46%): ¹H NMR (400 MHz, CDCl₃) δ 8.03 (m, 1H), 7.49 (m, 2H), 7.29 (m, 1H), 7.22 (m, 2H), 6.73 (d, J=16.0 Hz, 1H), 6.58 (dd, J=16.0, 7.8 Hz, 1H), 4.16 (m, 1H), 2.64 (s, 3H); ESIMS m/z 386.84 ([M−H]⁻); IR (thin film) 3428, 1690, 1113, 780 cm⁻¹.

(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoic acid (AI31)

The product was isolated as a white solid (500 mg, 50%): mp 91-93° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.02 (d, J=8.0 Hz, 1H), 7.35 (d, J=5.6 Hz, 1H), 7.30 (m, 3H), 6.61 (d, J=16.0 Hz, 1H), 6.48 (dd, J=16.0, 8.0 Hz, 1H), 4.13 (m, 1H), 2.65 (s, 3H); ESIMS m/z 406.87 ([M−H]⁻).

(E)-4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)benzoic acid (AI33)

The product was isolated as a white solid (500 mg, 45%): mp 142-143° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.97 (d, J=8.0 Hz, 1H), 7.77 (s, 1H), 7.65 (m, 1H), 7.41 (s, 2H), 6.68 (d, J=16.0 Hz, 1H), 6.53 (dd, J=16.0, 8.0 Hz, 1H), 4.16 (m, 1H); ESIMS m/z 474.87 ([M−H]⁻).

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic acid (AI69)

The title compound was isolated as a brown solid (0.8 g, 28%): ¹H NMR (400 MHz, CDCl₃) δ 13.42 (br, 1H), 7.98 (d, J=1.5 Hz, 1H), 7.94 (m, 2H), 7.75 (d, J=8.1 Hz, 1H), 7.65 (m, 1H), 7.06 (dd, J=15.9, 9.0 Hz, 1H), 6.80 (d, J=15.9 Hz, 1H), 4.91 (m, 1H); ESIMS m/z 484.75 ([M−H]⁻); IR (thin film) 3469, 1700 cm⁻¹.

(E)-2-Bromo-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoic acid (AI70)

The title compound was isolated as a yellow liquid (0.3 g, crude): ¹H NMR (300 MHz, CDCl₃) δ 7.79 (d, J=8.1 Hz, 1H), 7.67 (s, 1H), 7.34 (m, 3H), 6.56 (d, J=15.9 Hz, 1H), 6.45 (dd, J=15.9, 7.6 Hz, 1H), 4.43 (m, 1H); ESIMS m/z 471.0 ([M−H]⁻).

(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-ethylbenzoic acid (AI71)

The title compound was isolated as a brown gummy material (0.2 g, crude): ¹H NMR (300 MHz, DMSO-d₆) δ 12.5 (br, 1H), 7.85 (d, J=6.3 Hz, 2H), 7.75 (d, J=8.1 Hz, 1H), 7.52 (m, 2H), 6.96 (dd, J=8.7, 8.7 Hz, 1H), 6.78 (d, J=15.6 Hz, 1H), 4.80 (m, 1H), 4.06 (q, J=7.2 Hz, 2H), 1.33 (t, J=7.2 Hz, 3H); ESIMS m/z 419.06 ([M−H]⁻).

(E)-2-Chloro-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoic acid (AI72)

The title compound was isolated as a yellow liquid (0.7 g, 95%): ¹H NMR (300 MHz, CDCl₃) δ 7.85 (d, J=6.0 Hz, 1H), 7.46 (d, J=1.8 Hz, 1H), 7.41 (s, 3H), 6.57 (d, J=16.0 Hz, 1H), 6.45 (dd, J=16.0, 8.0 Hz, 1H), 4.16 (m, 1H); ESIMS m/z 455.0 ([M+H]⁺); IR (thin film) 1728, 1115, 817 cm⁻¹.

(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoic acid (AI73)

The title compound was isolated as a light brown gummy material (0.7 g, 38%): mp 91-93° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.02 (d, J=8.0 Hz, 1H), 7.35 (d, J=5.6 Hz, 1H), 7.30 (m, 3H), 6.10 (d, J=16.0 Hz, 1H), 6.46 (dd, J=16.0, 8.0 Hz, 1H), 4.03 (m, 1H), 2.65 (s, 3H); ESIMS m/z 406.87 ([M−H]⁻).

(E)-4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-fluorobenzoic acid (AI74)

The title compound was isolated as a light brown liquid (0.3 g, crude): ESIMS m/z 393.15 ([M−H]⁻).

(E)-2-Bromo-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)benzoic acid (AI75)

The title compound was isolated as a light brown liquid (0.35 g, crude): ESIMS m/z 451.91 ([M−H]⁻).

(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(methylthio)benzoic acid

¹H NMR (400 MHz, CDCl₃) δ 7.88-7.85 (m, 3H), 7.46 (d, J=6.8 Hz, 1H), 7.37 (s, 1H), 6.99 (dd, J=15.6, 8.8 Hz, 1H), 6.85 (d, J=16.0 Hz, 1H), 4.85-4.81 (m, 2H), 2.45 (s, 3H); ESIMS m/z 436.89 [(M−H)⁻]; IR (thin film) 3469, 1686, 1259, 714 cm⁻¹.

Prophetically, compounds AI34, AI36-AI41, AI44-AI45 (Table 1) could be made in accordance with the procedures disclosed in Example 10, or Examples 10 and 11.

Example 12: Preparation of (E)-4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methyl-N-(2,2,2-trifluoroethyl)benzamide (AC6)

To a stirred solution of (E)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoic acid in DMF was added 2,2,2-trifluoroethylamine, 1-hydroxybenzotriazole hydrate (HOBt.H₂O), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC.HCl) and N,N-diisopropylethylamine (DIEA), and the reaction mixture was stirred at 25° C. for 18 h. The reaction mixture was diluted with H₂O and extracted with EtOAc. The combined organic layer was washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 100-200 mesh; eluting with hexane:EtOAc afforded a white semi-solid (110 mg, 50%): ¹H NMR (400 MHz, CDCl₃) 7.40 (m, 2H), 7.26 (m, 3H), 6.56 (d, J=16.0 Hz, 1H), 6.48 (dd, J=16.0, 8.0 Hz, 1H), 5.82 (br s, 1H), 4.08 (m, 3H), 2.52 (s, 3H); ESIMS m/z 468.40 ([M−H]⁻); IR (thin film) 1657, 1113, 804 cm⁻¹.

Compounds AC7-AC38, AC40-AC58, AC110-AC112, AC117, and AC118 (Table 1) were made in accordance with the procedures disclosed in Example 12.

Example 13: Preparation of 4-((E)-3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methyl-N-((pyrimidin-5-yl)methyl)benzamide (AC39)

To a stirred solution of (pyrimidin-5-yl)methanamine (0.15 g, 1.43 mmol) in CH₂Cl₂ (10 mL) was added drop wise trimethylaluminum (2 M solution in toluene; 0.71 mL, 1.43 mmol), and the reaction mixture was stirred at 25° C. for 30 min. A solution of ethyl 4-((E)-3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoate (0.3 g, 0.71 mmol) in CH₂Cl₂ was added drop wise to the reaction mixture at 25° C. The reaction mixture was stirred at reflux for 18 h, cooled to 25° C., quenched with 0.5 N HCl solution (50 mL) and extracted with EtOAc (2×50 mL). The combined organic extracts were washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure. The crude compound was purified by flash chromatography (SiO₂, 100-200 mesh; eluting with 40% EtOAc in n-hexane) to afford the title compound (0.18 g, 55%): mp 141-144° C.; ¹H (400 MHz, CDCl₃) δ 9.19 (s, 1H), 8.79 (s, 2H), 7.37 (m, 2H), 7.23 (m, 2H), 7.21 (m, 1H), 6.57 (d, J=16.0 Hz, 1H), 6.40 (dd, J=16.0, 7.6 Hz 1H), 6.21 (m, 1H), 4.65 (s, 2H), 4.11 (m, 1H), 2.46 (s, 3H); ESIMS m/z 477.83 ([M−H]⁻).

Example 14: Preparation of (E)-2-Chloro-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (AC64)

To a stirred solution of glycine amide (0.15 g, 0.58 mmol) in CH₂Cl₂ (5 mL) was added trimethylaluminum (2 M solution in toluene; 1.45 mL, 2.91 mmol) dropwise, and the reaction mixture was stirred at 28° C. for 30 min. A solution of (E)-ethyl 2-chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoate (0.3 g, 0.58 mmol) in CH₂Cl₂ (5 mL) was added drop wise to the reaction mixture at 28° C. The reaction mixture was stirred at reflux for 18 h, cooled to 25° C., quenched with 1N HCl solution (50 mL) and extracted with CH₂Cl₂ (2×50 mL). The combined organic extracts were washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure. The crude compound was purified by flash chromatography (SiO₂, 100-200 mesh; eluting with 40% EtOAc in n-hexane) to afford the title compound as yellow solid (0.15 g, 50%): mp 83-85° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.72 (d, J=8.0 Hz, 1H), 7.44 (s, 1H), 7.40 (s, 2H), 7.36 (d, J=6.8 Hz, 1H), 7.05 (t, J=5.2 Hz, 1H), 6.70 (t, J=5.2 Hz, 1H), 6.57 (d, J=15.6 Hz, 1H), 6.44 (dd, J=15.6, 8.0 Hz, 1H), 4.23 (d, J=5.6 Hz, 2H), 4.15 (m, 1H), 4.01 (m, 2H); ESIMS m/z 580.72 ([M−H]⁻).

Compounds AC59-AC75 (Table 1) were made in accordance with the procedures disclosed in Example 14.

Example 15: Preparation of (E)-2-Bromo-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide (AC79)

To a stirred solution of (E)-2-bromo-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)benzoic acid (300 mg, 0.638 mmol) in DCM (5.0 mL) was added 2-amino-N-(2,2,2-trifluoroethyl)acetamide (172. mg, 0.638 mmol) followed by benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP) (364.5 mg, 0.701 mmol) and DIPEA (0.32 mL, 1.914 mmol), and the resultant reaction mixture was stirred at RT for 18 h. The reaction mixture was diluted with water and extracted with DCM. The combined DCM layer was washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 100-200 mesh; eluting with 40% ethyl acetate/petroleum ether) afforded the title compound as an off-white solid (121 mg, 31%): ¹H NMR (400 MHz, CDCl₃) δ 8.69 (t, J=6.0 Hz, 1H), 8.58 (t, J=6.0 Hz, 1H), 7.92 (s, 1H), 7.87 (d, J=6.4 Hz, 2H), 7.62 (d, J=8.4 Hz, 1H), 7.45 (d, J=8.4 Hz, 1H), 7.0 (m, 1H), 6.76 (d, J=15.6 Hz, 1H), 4.83 (t, J=8.0 Hz, 1H), 3.98 (m, 4H); ESIMS m/z 610.97 ([M+H]⁺); IR (thin film) 3303, 1658, 1166, 817 cm⁻¹.

Compounds AC76-AC80, AC96-AC102, and AC113 (Table 1) were made in accordance with the procedures disclosed in Example 15.

Example 16: Preparation of (E)-4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N-(1,1-dioxidothietan-3-yl)-2-fluorobenzamide (AC83)

To a stirred solution of (E)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-fluoro-N-(thietan-3-yl)benzamide (100 mg, 0.2159 mmol) in acetone/water (1:1, 5.0 mL) was added oxone (266 mg, 0.4319 mmol) and the resultant reaction mixture was stirred at RT for 4 h. The reaction mixture was diluted with water and extracted with ethyl acetate. The combined ethyl acetate layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 100-200 mesh; eluting with 30% ethyl acetate/pet ether) afforded the title compound as an off white solid (70.0 mg, 66%): ¹H NMR (400 MHz, CDCl₃) δ 8.07 (t, J=8.4 Hz, 1H), 7.39 (t, J=1.6 Hz, 1H), 7.31 (d, J=1.2 Hz, 1H), 7.26 (m, 2H), 7.23 (m, 2H), 7.19 (d, J=1.6 Hz, 1H), 6.60 (d, J=16.8 Hz, 1H), 6.49 (dd, J=16.8, 7.6 Hz, 1H), 4.90 (m, 1H), 4.64 (m, 2H), 4.14 (m, 2H); ESIMS m/z 493.83 ([M−H]⁻); IR (thin film) 1527, 1113, 801, 1167, 1321 cm⁻¹.

Compounds AC81-AC87 (Table 1) were made in accordance with the procedures disclosed in Example 16.

Example 17: Preparation of (E)-N-((5-Cyclopropyl-1,3,4-oxadiazol-2-yl)methyl)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-methylbenzamide (AC89)

A solution of (E)-N-(2-(2-(cyclopropanecarbonyl)hydrazinyl)-2-oxoethyl)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzamide (200 mg, 0.379 mmol) in POCl₃ (2.0 mL) was stirred at RT for 10 min, then the resultant reaction mixture was heated to 50° C. for 1 h. The reaction mixture was quenched with ice water at 0° C. and extracted with ethyl acetate. The combined ethyl acetate layer was washed with saturated NaHCO₃ solution and brine solution, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 100-200 mesh; eluting with 50% ethyl acetate/pet ether) afforded the title compound as a light brown gummy material (70.0 mg, 36%): ¹H NMR (400 MHz, CDCl₃) δ 7.43 (m, 2H), 7.27 (m, 2H), 7.23 (m, 2H), 6.58 (d, J=16.0 Hz, 1H), 6.41 (dd, J=16.0, 7.6 Hz, 1H), 4.79 (d, J=5.6 Hz, 2H), 4.14 (m, 1H), 2.48 (s, 3H), 2.18 (m, 1H), 1.16 (m, 4H); ESIMS m/z 509.89 ([M+H]⁺); IR (thin film) 1666, 1166, 1112, 800 cm⁻¹.

Example 18: Preparation of (E)-2-Bromo-N-(2-thioxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzothioamide (AC90)

To a stirred solution of (E)-2-bromo-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (400 mg, 0.638 mmol) in 5 mL of THF at RT was added 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide (Lawesson's reagent) (336 mg, 0.830 mmol) in one portion. The resulting reaction mixture was stirred for 18 h. TLC showed the reaction was not complete, therefore additional Lawesson's reagent (168 mg, 0.415 mmol) was added and reaction stirred for 48 h. After the reaction was deemed complete by TLC, the reaction mixture was concentrated under reduced pressure. Purification by flash chromatography (SiO₂, 230-400 mesh; eluting with 20% EtOAc in hexanes) afforded the title compound as a yellow glassy oil (188 mg, 44.7%): ¹H NMR (400 MHz, CDCl₃) δ 8.34 (m, 1H), 8.27 (m, 1H), 7.60 (d, J=1.6 Hz, 1H), 7.49 (d, J=8.0 Hz, 2H), 7.40 (s, 2H), 7.36 (dd, J=8.2, 1.7 Hz, 1H), 6.53 (d, J=16.0 Hz, 1H), 6.38 (dd, J=15.9, 7.9 Hz, 1H), 4.89 (d, J=8.4, 5.5 Hz, 2H), 4.48 (qd, J=9.0, 6.0 Hz, 2H), 4.11 (m, 1H); ESIMS m/z 656.9 ([M−H]⁻).

Example 19: Preparation of (E)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenylthioamido)-N-(2,2,2-trifluoroethyl)acetamide (AC91)

To a stirred solution of (E)-2-bromo-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (400 mg, 0.638 mmol) in 5 mL of THF at RT was added Lawesson's reagent (64.5 mg, 0.160 mmol) in one portion. The resulting reaction mixture was stirred for 18 h, after which time, the reaction mixture was concentrated under reduced pressure. Purification by flash chromatography (SiO₂, 230-400 mesh; eluting with 20% EtOAc in hexanes) afforded the title compounds as a yellow oil (18.5 mg, 4.51%): ¹H NMR (400 MHz, CDCl₃) δ 8.18 (t, J=5.0 Hz, 1H), 7.58 (d, J=1.6 Hz, 1H), 7.47 (d, J=8.0 Hz, 1H), 7.40 (s, 2H), 7.34 (dd, J=8.1, 1.6 Hz, 1H), 6.52 (m, 2H), 6.37 (dd, J=15.9, 7.9 Hz, 1H), 4.54 (d, J=4.9 Hz, 2H), 4.12 (m, 1H), 3.99 (qd, J=8.9, 6.5 Hz, 2H); ESIMS m/z 640.9 ([M−H]⁻).

The following compound was made in accordance with the procedures disclosed in Example 19.

(E)-2-Bromo-N-(2-thioxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (AC92)

The product was isolated as a colorless oil (17.9 mg, 4.36%): ¹H NMR (400 MHz, CDCl₃) δ 9.16 (d, J=6.1 Hz, 1H), 7.65 (d, J=1.6 Hz, 1H), 7.57 (d, J=8.0 Hz, 1H), 7.41 (m, 3H), 7.21 (t, J=5.6 Hz, 1H), 6.55 (d, J=15.9 Hz, 1H), 6.41 (dd, J=15.9, 7.8 Hz, 1H), 4.59 (d, J=5.6 Hz, 2H), 4.45 (qd, J=9.0, 6.0 Hz, 2H), 4.12 (q, J=7.2 Hz, 1H); ESIMS m/z 640.9 ([M−H]⁻).

Example 106: Preparation of Ethyl (Z) 2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoate (AI76)

The title compound was made in accordance with the procedure disclosed in Example 88 and was isolated as a yellow viscous oil (416 mg, 23%): ¹H NMR (400 MHz, CDCl₃) δ 7.80 (d, J=8.0 Hz, 1H), 7.40 (d, J=1.7 Hz, 1H), 7.35 (s, 2H), 7.12 (dd, J=8.0, 1.7 Hz, 1H), 6.86 (d, J=11.4 Hz, 1H), 6.23-5.91 (m, 1H), 4.42 (q, J=7.1 Hz, 2H), 4.33-4.10 (m, 1H), 1.42 (t, J=7.2 Hz, 3H); ¹⁹F NMR (376 MHz, CDCl₃) δ −69.34 (d, J=8.3 Hz); EIMS m/z 514.10 ([M]⁻); IR (thin film) 2983, 1727, 1247, 1204, 1116 cm⁻¹.

Example 107: Preparation of (Z)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoic acid (AI77)

To a stirred solution of (Z)-ethyl 2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoate (360 mg, 0.70 mmol) in CH₃CN (1.0 mL) was added iodotrimethylsilane (0.28 mL, 2.8 mmol). The reaction mixture was heated to reflux for 20 h, allowed to cool to ambient temperature and partitioned between CH₂Cl₂ and aq. 10% Na₂S₂O₃. Organic phase was washed once with aq. 10% Na₂S₂O₃ and dried over MgSO₄ and concentrated in vacuo. Passing the material through a silica plug with 10% EtOAc in hexanes, followed by 20% MeOH in CH₂Cl₂) as the eluting solvents afforded the title compound as a yellow foam (143 mg, 42%): mp 54-64° C.; ¹H NMR (400 MHz, CDCl₃) δ 11.36 (s, 1H), 7.99 (d, J=8.0 Hz, 1H), 7.43 (s, 1H), 7.30 (s, 2H), 7.14 (d, J=7.9 Hz, 1H), 6.85 (d, J=11.4 Hz, 1H), 6.15 (t, J=10.9 Hz, 1H), 4.36-4.09 (m, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −69.30.

Example 108: Preparation of (Z)-2-Bromo-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (AC95)

To a stirred solution of (Z)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoic acid (200 mg, 0.41 mmol) in anhydrous THF (5.0 mL) was added carbonyldiimidazole (82 mg, 0.51 mmol). The mixture was heated in a 50° C. oil bath for 1.5 h, treated with 2-amino-N-(2,2,2-trifluoroethyl)acetamide hydrochloride (109 mg, 0.057 mmol) and the resulting mixture heated to reflux for 8 h. After cooling to ambient temperature, the mixture was taken up in Et₂O and washed twice with aq. 5% NaHSO₄ (2×) and once with sat. NaCl (1×). After dying over MgSO₄, concentration in vacuo and purification by medium pressure chromatography on silica with EtOAc/Hexanes as the eluents, the title compound was obtained as a white foam (160 mg, 41%) mp 48-61° C.: ¹H NMR (400 MHz, CDCl₃) δ 7.58 (d, J=7.9 Hz, 1H), 7.44-7.29 (m, 3H), 7.14 (dd, J=7.9, 1.6 Hz, 1H), 6.86 (d, J=11.4 Hz, 1H), 6.76 (t, J=5.9 Hz, 1H), 6.59 (br s, 1H), 6.21-6.04 (m, 1H), 4.23 (d, J=5.5 Hz, 1H), 3.98 (qd, J=9.0, 6.5 Hz, 2H); ¹⁹F NMR (376 MHz, CDCl₃) δ −69.31, −72.3; EIMS m/z 626.9 ([M+1]⁺).

Example 109a: Preparation of (E)-2-Bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (AC114)

(E)-tert-Butyl 4-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamido)piperidine-1-carboxylate (0.75 g, 1.11 mmol) was added to dioxane HCl (10 mL) at 0° C. and was stirred for 18 h. The reaction mixture was concentrated under reduced pressure and triturated with diethylether to afford the compound as a light brown solid (0.6 g, 88%).

Example 109b: Preparation of (E)-N-(1-Acetylpiperidin-4-yl)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (AC103)

To a stirred solution of (E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide (0.1 g, 0.16 mmol) in DCM (10.0 mL) was added triethylamine (0.046 mL, 0.35 mmol) and stirred for 10 min. Then acetyl chloride (0.014, 0.18 mmol) was added and stirred for 16 h at RT. The reaction mixture was diluted with DCM and washed with saturated NaHCO₃ solution and brine solution. The combined DCM layer was dried over Na₂SO₄ and concentrated under reduced pressure to afford crude compound. The crude compound was washed with 5% diethyl ether/n-pentane to afford the title compound as a white solid (0.054 g, 50%).

Example 110: Preparation of (E)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N-(1-(3,3,3-trifluoropropanoyl)piperidin-4-yl)benzamide (AC104)

To a stirred solution of 3,3,3-trifluoropropanoic acid (0.02 g, 0.16 mmol) in DCM (10.0 mL), (E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide (0.1 g, 0.16 mmol), PYBOP (0.09 g, 0.17 mmol), and DIPEA (0.06 g, 0.48 mmol) were added at RT. The reaction mixture was stirred at RT for 5 h. The reaction mixture was diluted with DCM. The combined DCM layer was washed with 3N HCl and saturated NaHCO₃ solution, the separated DCM layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford crude compound. The crude compound was purified by column chromatography (SiO₂, 100-200 mesh; eluting with 2% methanol in DCM) to afford the title compound as an off white gummy material (0.035 g, 29.%).

Example 111: Preparation of (E)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)benzamide (AC105)

To a stirred solution of (E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide (0.1 g, 0.16 mmol) in THF (5.0 mL) was added triethylamine (0.06 mL, 0.64 mmol) and stirred for 10 min. Then 2,2,2-trifluoroethyl triflluoromethanesulfonate (0.03, 0.16 mmol) was added and stirred for 16 h at RT. The reaction mixture was diluted with ethyl acetate and washed with saturated NaHCO₃ solution and brine solution. The combined ethyl acetate layer was dried over Na₂SO₄ and concentrated under reduced pressure to afford the title compound as a brown solid (0.05 g, 44%).

Example 112: Preparation of (E)-2-Bromo-N-(1-methylpiperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (AC106)

A solution of (E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide (0.1 g, 0.16 mmol), formaldehyde (30% in water) (0.1 mL, 0.16 mmol) and acetic acid (0.01 mL) in methanol (5.0 mL) was stirred at RT for 30 min. After that NaBH₃CN (0.01 g, 0.16 mmol) was added at 0° C. and the reaction was stirred for 8 h at RT. The solvent was removed under reduced pressure to obtain residue which was diluted with ethyl acetate and washed with saturated aq. NaHCO₃ solution and brine solution. The combined ethyl acetate layer was dried over Na₂SO₄ and concentrated under reduced pressure to obtain a residue, which was triturated with diethyl ether/pentane to afford the title compound as a pale yellow gummy material (0.06 g, 59%).

Example 113: Preparation of ((E)-2-Bromo-N-(1-(cyanomethyl)piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (AC107)

To a stirred solution of (E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide (0.25 g, 0.43 mmol) in THF (10.0 mL) was added triethylamine (0.16 mL, 1.29 mmol) and the reaction was stirred for 10 min. Then 2-bromoacetonitrile (0.07, 0.65 mmol) was added and the reaction was stirred for 8 h at RT. The reaction mixture was diluted with ethyl acetate and washed with saturated brine solution. The combined ethyl acetate layer was dried over Na₂SO₄ and concentrated under reduced pressure to afford the title compound as an off-white solid (0.125 g, 46.8%).

Example 114: Preparation of (E)-2-Bromo-N-(1-(oxetan-3-yl)piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (AC108)

A solution of (E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide (0.2 g, 0.35 mmol), oxetan-3-one (0.027 g, 0.38 mmol) and acetic acid (0.01 mL) in methanol (5.0 mL) was stirred at RT for 30 min. After that NaBH₃CN (0.022 g, 0.35 mmol) was added at 0° C. slowly lot wise over the period of 10 min and the reaction was stirred for 8 h at RT. The solvent was removed under reduced pressure to obtain a residue which was diluted with ethyl acetate and washed with saturated NaHCO₃ solution and brine solution. The combined ethyl acetate layer was dried over Na₂SO₄ and concentrated under reduced pressure to obtain a residue, which was triturated with diethyl ether/pentane to afford the title compound as an off-white solid (0.05 g, 23%).

Example 115: Preparation of (E)-2-Bromo-N-(1-(2-hydroxyethyl)piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (AC109)

To a stirred solution of (E)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamide (0.25 g, 0.43 mmol) in THF (10.0 mL) was added triethylamine (0.16 mL, 1.29 mmol) and the reaction was stirred for 10 min. Then 2-chloroethanol (0.05, 0.65 mmol) was added and the reaction was stirred for 8 h at RT. The reaction mixture was diluted with ethyl acetate and washed with saturated brine solution. The combined ethyl acetate layer was dried over Na₂SO₄ and concentrated under reduced pressure to afford the title compound as an off-white solid (0.09 g, 34%).

Example 116: Preparation of (E)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamido)acetic acid (AI78)

To a stirred solution of (E)-tert-butyl 2-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamido)acetate (440 mg, 0.734 mmol) in DCM (36.0 ml), was added TFA (4.0 mL) and the reaction mixture was stirred at RT for 1 h. The reaction mixture was concentrated under reduced pressure to obtain residue which was washed with n-pentane to afford the title compound as an off-white solid (310 mg, 78%): ¹H NMR (400 MHz, CDCl₃) δ 13.0 (s, 1H), 8.75 (t, J=5.7 Hz, 1H), 7.93 (m, 2H), 7.62 (d, J=7.5 Hz, 1H), 7.40 (d, J=8.1 Hz, 1H), 6.96 (dd, J=15.3, 9.3 Hz, 1H), 6.78 (d, J=15.3 Hz, 1H), 4.83 (m, 1H), 3.90 (d, J=5.7 Hz, 2H); ESIMS m/z 543.61 ([M+H]⁺); IR (thin film) 3429, 1635, 1114, 772 cm⁻¹.

Example 117: Preparation of (E)-N-((6-Chloropyridin-3-yl)methyl)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-methylbenzothioamide (AC115)

To the stirred solution of (E)-N-((6-chloropyridin-3-yl)methyl)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzamide (0.06 g, 0.117 mmol) in toluene (3 mL) was added Lawesson's reagent (0.14 g, 0.351 mmol) and the reaction was irradiated at 100° C. for 1 h, then cooled to RT and concentrated under reduced pressure to provide crude compound. The crude product was purified by preparative HPLC to afford the product as yellow color solid (0.03 g, 49%).

Example 118: Preparation of (E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2-(trifluoromethoxy)benzamide (AC116)

Step 1. 2-(Trifluoromethoxy)-4-vinylbenzoic acid (AI79)

To a stirred solution of 4-bromo-2-(trifluoromethoxy)benzoic acid (1 g, 3.67 mmol) in DMSO (20 mL) was added potassium vinyltrifluoroborate (1.47 g, 11.02 mmol) and potassium carbonate (1.52 g, 11.02 mmol). The reaction mixture was degassed with argon for 30 min Bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride (0.13 g, 0.18 mmol) was added and the reaction mixture was heated to 80° C. for 1 h. The reaction mixture was diluted with water (100 mL), extracted with ethyl acetate (2×50 mL), washed with brine, and dried over Na₂SO₄. Concentration under reduced pressure furnished the crude compound which was purified by flash column chromatography to afford the product as pale yellow gummy material (0.4 g, 47%): ¹H NMR (400 MHz, CDCl₃) δ 8.05 (d, J=8.1 Hz, 1H), 7.44 (d, J=1.8 Hz, 1H), 7.35 (s, 1H), 6.78 (dd, J=17.4.1, 11.1 Hz, 1H), 5.92 (d, J=17.4 Hz, 1H), 5.51 (d, J=10.8 Hz, 1H); ESIMS m/z 232.97 ([M+H]⁺).

Step 2. (E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-(trifluoromethoxy)benzoic acid (AI80)

To a stirred solution of 2-(trifluoromethoxy)-4-vinylbenzoic acid (0.356 g, 1.53 mmol) in 1N methyl pyrrolidine (5.0 mL) was added 1-(1-bromo-2,2,2-trifluoroethyl)-3,5-dichloro 4-fluorobenzene (1.0 g, 3.07 mmol), copper(I) chloride (CuCl; 0.03 g, 0.307 mmol) and 2,2 bipyridyl (0.095 g, 0.614 mmol). The reaction mixture was stirred at 150° C. for 1 h. After the reaction was complete by TLC, the reaction mixture was diluted with water (100 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure to obtain the crude compound which was purified by flash column chromatography to afford the product as pale yellow gummy material (0.3 g, 21%): ¹H NMR (400 MHz, CDCl₃) δ 8.08 (d, J=8.0 Hz, 1H), 7.45 (d, J=1.6 Hz, 1H), 7.35 (s, 3H), 6.63 (d, J=16.0 Hz, 1H), 6.50 (dd, J=16.0, 8.0 Hz, 1H), 4.15 (m, 1H); ESIMS m/z 474.81 ([M−H]⁻).

Step 3. (E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)-2-(trifluoromethoxy)benzamide (AC116)

A mixture of (E)-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-(trifluoromethoxy)benzoic acid (0.25 g, 0.52 mmol), 2-amino-N-(2,2,2-trifluoroethyl)acetamide (0.158 g, 0.62 mmol), PyBOP (0.40 g, 0.78 mmol) and DIPEA (0.134 g, 1.04 mmol) in DCM (10.0 mL) were stirred at RT for 16 h. The reaction mixture was diluted with water and extracted with DCM. The combined DCM layer was washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 100-200 mesh; eluting with 20% ethyl acetate/pet ether) afforded the title compound as a pale yellow gummy material (0.15 g, 47%).

The following molecules were made in accordance with the procedures disclosed in Example 118, Step 2:

(E)-4-(3-(3,5-Dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-methylbenzoic acid

The title molecule was isolated as a brown solid: ¹H NMR (400 MHz, DMSO-d₆) δ 12.90 (bs, 1H), 7.85 (s, 1H), 7.78-7.75 (m, 3H), 7.47-7.41 (m, 2H), 6.89 (dd, J=15.6, 9.2 Hz, 1H), 6.72 (d, J=15.6 Hz, 1H), 4.80-4.75 (m, 1H), 2.33 (s, 3H); ESIMS m/z 474.90 ([M−H]⁻); IR (thin film) 3437, 1689, 1165, 579 cm⁻¹.

(E)-4-(3-(3,5-Dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown solid: ¹H NMR (300 MHz, DMSO-d₆) δ 13.5 (bs, 1H), 8.03 (s, 1H), 7.95-7.85 (m, 4H), 7.81 (d, J=7.8 Hz, 1H), 7.14 (dd, J=15.6, 9.6 Hz, 1H), 6.90 (d, J=15.9 Hz, 1H), 4.86-4.79 (m, 1H); ESIMS m/z 528.82 ([M−H]⁺); IR (thin film) 3437, 1707, 1153, 555 cm⁻¹.

(E)-2-Bromo-4-(3-(3,5-dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown liquid: ¹H NMR (400 MHz, DMSO-d₆) δ 13.90 (bs, 1H), 7.98 (s, 1H), 7.88 (s, 1H), 7.84 (s, 2H), 7.74 (d, J=7.6 Hz, 1H), 7.64 (d, J=8.8 Hz, 1H), 7.04 (dd, J=15.6, 8.8 Hz, 1H), 6.78 (d, J=15.6 Hz, 1H), 4.80-4.78 (m, 1H); ESIMS m/z 538.74 ([M−H]⁻); IR (thin film) 3424, 1695, 1168, 578 cm⁻¹.

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3-fluoro-5-(trifluoromethyl)phenyl)but-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown liquid: ¹H NMR (400 MHz, DMSO-d₆) δ 13.3 (bs, 1H), 7.93 (s, 1H), 7.82-7.77 (m, 2H), 7.72-7.66 (m, 2H), 7.59 (d, J=8.0 Hz, 1H), 7.03 (dd, J=15.6, 9.2 Hz, 1H), 6.76 (d, J=15.6 Hz, 1H), 4.94-4.90 (m, 1H); ESIMS m/z 469.02 ([M−H]⁻); IR (thin film) 3444, 1704, 1172, 513 cm⁻¹.

(E)-4-(3-(3,5-Bis(trifluoromethyl)phenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-bromobenzoic acid

The title molecule was isolated as a brown solid: ¹H NMR (400 MHz, CDCl₃) δ 7.98 (d, J=7.6 Hz, 1H), 7.92 (s, 1H), 7.83 (s, 2H), 7.73 (d, J=1.6 Hz, 1H), 7.42-7.40 (m, 1H), 6.62 (d, J=16.4 Hz, 1H), 6.55 (dd, J=16.0, 8.0 Hz, 1H), 4.40-4.30 (m, 1H); ESIMS m/z 518.94 ([M−H]⁻); IR (thin film) 3447, 1705, 1171, 526 cm⁻¹.

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3-(trifluoromethyl)phenyl)but-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 13.50 (bs, 1H), 7.97-7.87 (m, 3H), 7.78-7.61 (m, 4H), 7.08 (dd, J=15.9, 9.3 Hz, 1H), 6.81 (d, J=15.9 Hz, 1H), 4.97-4.84 (m, 1H); ESIMS m/z 518.94 ([M−H]⁻); IR (thin film) 3447, 1705, 1171, 526 cm⁻¹.

(E)-2-Bromo-4-(3-(3-chloro-5-(trifluoromethyl)phenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a pale yellow gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.9 (s, 1H), 8.03 (s, 1H), 7.96-7.91 (m, 3H), 7.72 (d, J=8.1 Hz, 1H), 7.63-7.60 (m, 1H), 7.11 (dd, J=15.9, 9.6 Hz, 1H), 6.79 (d, J=15.9 Hz, 1H), 4.98-4.91 (m, 1H); ESIMS m/z 484.94 ([M−H]⁻); IR (thin film) 3444, 1705, 1171, 764 cm⁻¹.

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(4-fluoro-3-(trifluoromethyl)phenyl)but-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown liquid: ¹H NMR (300 MHz, CDCl₃) δ 8.00 (d, J=8.1 Hz, 1H), 7.71 (s, 1H), 7.61-7.59 (m, 2H), 7.41 (d, J=8.1 Hz, 1H), 7.30-7.24 (m, 1H), 6.59 (dd, J=16.2, 6.0 Hz, 1H), 6.48 (d, J=16.5 Hz, 1H), 4.26-4.21 (m, 1H); ESIMS m/z 469.0 ([M−H]⁻); IR (thin film) 3444, 1699, 1327 cm⁻¹.

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trifluorophenyl)but-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.60 (bs, 1H), 7.97 (s, 2H), 7.72 (d, J=7.2 Hz, 1H), 7.41-7.31 (m, 2H), 7.04 (dd, J=15.6, 9.0 Hz, 1H), 6.71 (d, J=15.9 Hz, 1H), 4.15-4.11 (m, 1H); ESIMS m/z 438.8 ([M+H]⁺).

(E)-4-(4,4,4-Trifluoro-3-(2,3,4-trifluorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 8.00 (s, 1H), 7.93 (d, J=8.4 Hz, 1H), 7.81 (d, J=8.1 Hz, 1H), 7.63-7.60 (m, 1H), 7.47-7.44 (m, 1H), 7.02-7.01 (m, 1H), 5.10-4.90 (m, 1H).

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(2,3,4-trifluorophenyl)but-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum and the crude acid was taken on directly to the next step: ¹H NMR (300 MHz, DMSO-d₆) δ 13.65 (bs, 1H), 7.95 (s, 1H), 7.75 (d, J=7.8 Hz, 1H), 7.62-7.59 (m, 2H), 7.50 (dd, J=15.6, 9.0 Hz, 1H), 6.95 (d, J=15.9 Hz, 1H), 4.86-4.74 (m, 1H); ESIMS m/z 436.92 ([M−H]⁻); IR (thin film) 3445, 1641, 1116 cm⁻¹.

(E)-4-(4,4,4-Trifluoro-3-(2,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.6 (s, 1H), 8.04 (s, 1H), 7.96 (d, J=8.4 Hz, 3H), 7.83 (d, J=8.1 Hz, 1H), 7.17-7.03 (m, 2H), 5.16-5.05 (m, 1H); ESIMS m/z 476.9 ([M−H]⁻); IR (thin film) 3436, 1651, 1116, 661 cm⁻¹.

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(2,4,5-trichlorophenyl)but-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.4 (s, 1H), 7.99 (d, J=10.2 Hz, 3H), 7.76 (d, J=8.1 Hz, 1H), 7.65 (d, J=7.8 Hz, 1H), 7.09-6.91 (m, 2H), 5.11-5.05 (m, 1H); ESIMS m/z 486.8 ([M−H]⁻); IR (thin film) 3436, 1651, 1115, 737 cm⁻¹.

(E)-4-(3-(4-Chloro-3-nitrophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown gum and the crude acid was taken on directly to the next step: ¹H NMR (300 MHz, DMSO-d₆) 13.80 (bs, 1H), 8.33 (s, 1H), 7.94-7.81 (m, 5H), 7.75-7.72 (m, 1H), 7.06 (dd, J=15.9, 8.7 Hz, 1H), 6.90 (d, J=15.9 Hz, 1H), 5.02-4.81 (m, 1H).

(E)-2-Bromo-4-(3-(4-chloro-3-nitrophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) 13.50 (bs, 1H), 8.31 (s, 1H), 8.00-7.77 (m, 3H), 7.75-7.72 (m, 1H), 7.63-7.55 (m, 1H), 7.03 (dd, J=15.9, 9.0 Hz, 1H), 6.81 (d, J=15.9 Hz, 1H), 5.04-4.91 (m, 1H); ESIMS m/z 462.16 ([M−H]⁻); IR (thin film) 3428, 1697, 1113, 749 cm⁻¹.

(E)-4-(4,4,4-Trifluoro-3-(4-fluoro-3,5-dimethylphenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 7.96 (s, 1H), 7.92 (d, J=8.4 Hz, 1H), 7.80-7.75 (m, 1H), 7.27 (d, J=6.9 Hz, 2H), 6.96 (dd, J=15.6, 8.7 Hz, 1H), 6.87 (d, J=15.6 Hz, 1H), 4.68-4.56 (m, 1H), 2.23 (s, 6H); ESIMS m/z 419.03 ([M−H]⁻); IR (thin film) 3445, 2928, 1713, 1146 cm⁻¹.

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(4-fluoro-3,5-dimethylphenyl)but-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 7.91 (s, 1H), 7.74 (d, J=7.8 Hz, 1H), 7.61-7.58 (m, 1H), 7.26 (d, J=6.6 Hz, 2H), 6.93 (dd, J=15.9, 8.7 Hz, 1H), 6.87 (d, J=15.9 Hz, 1H), 4.59-4.53 (m, 1H), 2.23 (s, 6H); ESIMS m/z 428.97 ([M−H]⁻); IR (thin film) 3473, 1701, 1111, 581 cm⁻¹.

(E)-4-(4,4,4-Trifluoro-3-(4-fluoro-3-methylphenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 13.58 (bs, 1H), 7.98 (s, 1H), 7.92-7.90 (m, 1H), 7.80 (d, J=8.1 Hz, 1H), 7.48-7.45 (m, 1H), 7.42-7.37 (m, 1H), 7.22-7.16 (m, 1H), 7.04 (dd, J=15.9, 8.7 Hz, 1H), 6.88 (d, J=15.9 Hz, 1H), 4.70-4.60 (m, 1H), 4.04-3.99 (m, 1H), 2.26 (s, 3H); ESIMS m/z 405.05 ([M−H]⁻); IR (thin film) 3437, 1710, 1145 cm⁻¹.

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(4-fluoro-3-methylphenyl)but-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 13.39 (bs, 1H), 7.91 (s, 1H), 7.72 (d, J=8.1 Hz, 1H), 7.61-7.58 (m 1H), 7.47-7.44 (m, 1H), 7.38-7.36 (m, 1H), 7.18 (t, J=9.6 Hz, 1H), 6.95 (dd, J=15.6, 8.7 Hz, 1H), 6.76 (d, J=15.9 Hz, 1H), 4.67-4.61 (m, 1H), 2.25 (s, 3H); ESIMS m/z 415.0 ([M−H]⁻); IR (thin film) 3435, 2989, 1700, 1260 cm⁻¹.

(E)-4-(3-(3,5-Dichlorophenyl)-4,4,5,5,5-pentafluoropent-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown semi solid: ¹H NMR (400 MHz, DMSO-d₆) δ 13.70 (bs, 1H), 8.01 (s, 1H), 7.91 (s, 1H), 7.80 (d, J=8.4 Hz, 1H), 7.72 (J=1.6 Hz, 2H), 7.66 (t, J=3.2 Hz, 1H), 7.15 (dd, J=15.6, 9.6 Hz, 1H), 6.91 (d, J=15.6 Hz, 1H), 4.86-4.78 (m, 1H); ESIMS m/z 491.0 ([M−H]⁻); IR (thin film) 3446, 1712, 1141, 749 cm⁻¹.

(E)-2-Bromo-4-(3-(3,5-dichlorophenyl)-4,4,5,5,5-pentafluoropent-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (400 MHz, DMSO-d₆) δ 7.85 (s, 1H), 7.70 (s, 2H), 7.65-7.64 (m, 1H), 7.56-7.52 (m, 2H), 6.94 (d, J=9.2 Hz, 1H), 6.76 (d, J=16 Hz, 1H), 4.82-4.80 (m, 1H); ESIMS m/z 500.8 ([M−H]⁻); IR (thin film) 3422, 1683, 1184, 750, 575 cm⁻¹.

(E)-4-(3-(3,4-Dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.5 (bs, 1H), 8.01-7.99 (m, 2H), 7.94-7.91 (m, 1H), 7.85-7.78 (m, 2H), 7.53-7.50 (m, 1H), 7.09 (dd, J=15.6, 8.7 Hz, 1H), 6.89 (d, J=15.9 Hz, 1H), 4.85-4.78 (m, 1H); ESIMS m/z 528.8 ([M−H]⁻); IR (thin film) 3437, 1722, 1168 cm⁻¹.

(E)-2-Bromo-4-(3-(3,4-dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.38 (bs, 1H), 7.98-7.96 (m, 2H), 7.84 (d, J=8.4 Hz, 1H), 7.74 (d, J=8.1 Hz, 1H), 7.63-7.61 (m, 1H), 7.51-7.49 (m, 1H), 7.01 (dd, J=15.9, 9.0 Hz, 1H), 6.78 (d, J=15.6 Hz, 1H), 4.82-4.76 (m, 1H); ESIMS m/z 538.8 ([M−H]⁻); IR (thin film) 3446, 1699, 1166, 581 cm⁻¹.

(E)-4-(4,4,4-Trifluoro-3-(3-(trifluoromethoxy)phenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown semi solid: ¹H NMR (300 MHz, DMSO-d₆) δ 8.01 (s, 1H), 7.94 (d, J=8.7 Hz, 1H), 7.80 (d, J=8.1 Hz, 1H), 7.63-7.55 (m, 3H), 7.41 (d, J=7.5 Hz, 1H), 7.11 (dd, J=15.6, 9.0 Hz, 1H), 6.92 (d, J=15.9 Hz, 1H), 4.89-4.82 (m, 1H); ESIMS m/z 456.98 ([M−H]⁻); IR (thin film) 3413, 1668, 1161 cm⁻¹.

(E)-2-Bromo-4-(4,4,4-trifluoro-3-(3-(trifluoromethoxy)phenyl)but-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown solid: ¹H NMR (300 MHz, DMSO-d₆) δ 7.73 (s, 1H), 7.59 (m, 3H), 7.44 (s, 1H), 7.40 (d, J=7.6 Hz, 2H), 6.88 (dd, J=15.6, 9.0 Hz, 1H), 6.73 (d, J=15.9 Hz, 1H), 4.85-4.82 (m, 1H); ESIMS m/z 466.93 ([M−H]⁻); IR (thin film) 3437, 1703, 1111 cm⁻¹.

(E)-4-(3-(3-Cyano-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 13.60 (bs, 1H), 8.21-8.19 (m, 1H), 8.01-7.91 (m, 3H), 7.81 (d, J=8.4 Hz, 1H), 7.12 (dd, J=15.9, 8.1 Hz, 1H), 6.91 (d, J=15.6 Hz, 1H), 4.92-4.86 (m, 1H); ESIMS m/z 416.27 ([M−H]⁻); IR (thin film) 3429, 2238, 1713, 1116 cm⁻¹.

(E)-2-Bromo-4-(3-(3-cyano-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.56 (bs, 1H), 8.21-8.18 (m, 1H), 8.00-7.95 (m, 2H), 7.73-7.59 (m, 3H), 7.03 (dd, J=15.9, 9.3 Hz, 1H), 6.79 (d, J=15.3 Hz, 1H), 4.87-4.84 (m, 1H); ESIMS m/z 426.0 ([M−H]⁻).

(E)-2-Bromo-4-(3-(3,4-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.4 (s, 1H), 7.96 (d, J=1.2 Hz, 1H), 7.88 (d, J=1.8 Hz, 1H), 7.74-7.68 (m, 2H), 7.63 (dd, J=8.1, 1.2 Hz, 1H), 7.57 (dd, J=8.4, 1.8 Hz, 1H), 7.02 (dd, J=15.9, 9.3 Hz, 1H), 6.78 (dd, J=5.9 Hz, 1H), 4.84-4.78 (m, 1H); ESIMS m/z 451.0 ([M−H]⁻); IR (thin film) 3445, 1704, 1113, 740 cm⁻¹.

(E)-4-(3-(3-Bromo-5-chlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown solid: ¹H NMR (300 MHz, DMSO-d₆) δ 13.50 (bs, 1H), 7.91 (s, 1H), 7.86-7.64 (m, 5H), 7.06 (dd, J=15.9, 9.0 Hz, 1H), 6.87 (d, J=15.9 Hz, 1H), 4.85-4.78 (m, 1H); ESIMS m/z 485.17 ([M−H]⁻); IR (thin film) 3438, 1708, 1114, 774, 516 cm⁻¹.

(E)-2-Bromo-4-(3-(3-bromo-5-chlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.38 (bs, 1H), 7.98 (s, 1H), 7.80-7.72 (m, 4H), 7.64-7.61 (m, 1H), 7.06 (dd, J=15.9, 9.3 Hz, 1H), 6.79 (d, J=15.6 Hz, 1H), 4.88-4.80 (m, 1H); ESIMS m/z 495.05 ([M−H]⁻); IR (thin film) 3436, 1699, 1116, 750, 531 cm⁻¹.

(E)-4-(3-(3-Bromo-5-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 13.6 (bs, 1H), 8.02 (s, 1H), 7.91-7.89 (m, 1H), 7.81 (d, J=8.0 Hz, 1H), 7.69 (s, 1H), 7.63-7.59 (m, 1H), 7.55 (d, J=9.3 Hz, 1H), 7.11 (dd, J=15.9, 9.0 Hz, 1H), 6.91 (d, J=15.9 Hz, 1H), 4.87-4.80 (m, 1H); ESIMS m/z 469.07 ([M−H]⁻); IR (thin film) 3428, 1712, 1171, 523 cm⁻¹.

(E)-4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoic acid

The title molecule was isolated as a yellow solid: ¹H NMR (400 MHz, CDCl₃) δ 8.18-8.03 (m, 2H), 7.49 (d, J=8.3 Hz, 2H), 7.42 (s, 2H), 6.66 (d, J=15.9 Hz, 1H), 6.47 (dd, J=15.9, 8.0 Hz, 1H), 4.13 (p, J=8.6 Hz, 1H); ¹⁹F NMR (376 MHz, CDCl₃) δ −68.65; ESIMS m/z 409.1 ([M−H]⁻).

(E)-2-Bromo-4-(3-(3-chloro-4-methylphenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 13.30 (bs, 1H), 7.93 (d, J=1.2 Hz, 1H), 7.42 (d, J=8.1 Hz, 1H), 7.62 (dd, J=1.5, 8.1 Hz, 1H), 7.53 (s, 1H), 7.48 (d, J=7.8 Hz, 1H), 7.39 (d, J=7.8 Hz, 1H), 6.96 (dd, J=15.6, 8.7 Hz, 1H), 6.77 (d, J=15.6 Hz, 1H), 4.73-4.61 (m, 1H), 2.35 (s, 3H); ESIMS m/z 431.77 ([M−H]⁻); IR (thin film) 3435, 1701, 1111, 750 cm⁻¹.

(E)-4-(3-(3-Chloro-4-methylphenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.50 (bs, 1H), 7.98 (s, 1H), 7.92 (d, J=8.1 Hz, 1H), 7.80 (d, J=8.1 Hz, 1H), 7.53 (s, 1H), 7.48 (d, J=8.1 Hz, 1H), 7.40 (d, J=8.4 Hz, 1H), 7.04 (dd, J=15.6, 8.4 Hz, 1H), 6.88 (d, J=15.6 Hz, 1H), 4.72-4.66 (m, 1H), 2.35 (s, 3H); ESIMS m/z 421.82 ([M−H]⁻); IR (thin film) 3460, 2926, 1712, 1170, 750 cm⁻¹.

(E)-4-(4,4,5,5,5-Pentafluoro-3-(3,4,5-trichlorophenyl)pent-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as a dark brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.6 (bs, 1H), 8.03 (s, 1H), 7.95-7.86 (m, 3H), 7.81 (d, J=8.1 Hz, 1H), 7.16 (dd, J=15.3, 9.3 Hz, 1H), 6.92 (d, J=15.6 Hz, 1H), 4.95-4.88 (m, 1H); ¹⁹F NMR (300 MHz, DMSO-d₆) δ −80.35, −58.02; ESIMS m/z 526.8 ([M+H]⁺).

(E)-2-Bromo-4-(4,4,5,5,5-pentafluoro-3-(3,4,5-trichlorophenyl)pent-1-en-1-yl)benzoic acid

The title molecule was isolated as a dark brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.6 (bs, 1H), 7.94 (s, 2H), 7.78 (d, J=7.8 Hz, 1H), 7.71 (d, J=7.8 Hz, 1H), 7.60 (d, J=7.5 Hz 1H), 7.07 (dd, J=15.0, 8.7 Hz, 1H), 6.79 (d, J=15.6 Hz, 1H), 4.93-4.78 (m, 1H); ESIMS m/z 538.9 ([M+H]⁺); IR (thin film) 3420, 1602, 1123, 746 cm⁻¹.

(E)-2-Bromo-4-(3-(4-cyano-3,5-difluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown gum: ESIMS m/z 443.91 ([M−H]⁻); IR (thin film) 3447, 2244, 1703, 1114 cm⁻¹.

(E)-2-Chloro-4-(3-(3,5-dibromophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a brown liquid: ¹H NMR (300 MHz, DMSO-d₆) δ 13.39 (bs, 1H), 7.95-7.70 (m, 5H), 7.61 (d, J=8.1 Hz, 1H), 7.07 (dd, J=15.6, 9.3 Hz, 1H), 6.80 (d, J=15.6 Hz, 1H), 4.84-4.78 (m, 1H); ESIMS m/z 496.77 ([M−H]⁻); IR (thin film) 3439, 2920, 1707, 1165 cm⁻¹.

(E)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated as an off white solid: mp 140-143° C.; ¹H NMR (400 MHz, DMSO) δ 13.60 (bs, 1H), 8.02 (s, 1H), 7.94-7.90 (m, 1H), 7.88-7.86 (m, 2H), 7.81-7.79 (m, 1H), 7.12 (dd, J=15.6, 8.8 Hz, 1H), 6.89 (d, J=15.6 Hz, 1H), 4.86-4.81 (m, 2H); ESIMS m/z 458.88 ([M−H]⁻).

(E)-4-(3-(3,4-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzoic acid

The title molecule was isolated as a light orange crystalline solid (875 mg, 88%): ¹H NMR (400 MHz, CDCl₃) δ 12.35 (s, 1H), 8.08 (d, J=8.4 Hz, 2H), 7.55-7.41 (m, 4H), 7.24 (dd, J=8.3, 2.1 Hz, 1H), 6.64 (d, J=15.8 Hz, 1H), 6.51 (dd, J=15.9, 7.7 Hz, 1H), 4.15 (p, J=8.7 Hz, 1H); ¹⁹F NMR 376 MHz, CDCl₃) δ −68.75; ESIMS m/z 375 ([M+H]⁺).

(E)-4-(3-(3,4-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated was isolated as a brown gum: ¹H NMR (400 MHz, DMSO-d₆) δ 13.6 (s, 1H), 8.02 (s, 1H), 7.93-7.89 (m, 2H), 7.80 (d, J=7.6 Hz, 1H), 7.73 (d, J=8.4, Hz, 1H), 7.58 (dd, J=8.4, 2.0 Hz, 1H), 7.09 (dd, J=15.6, 8.8, Hz, 1H), 6.89 (d, J=15.6, Hz, 1H), 4.86-4.81 (m, 1H); ESIMS m/z 441.0 ([M−H]⁻); IR (thin film) 3447, 1710, 1169, 749 cm⁻¹.

(E)-4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)benzoic acid

The title molecule was isolated was isolated as a brown gum: ¹H NMR (300 MHz, DMSO-d₆) δ 13.6 (bs, 1H), 7.98 (s, 1H), 7.91 (d, J=7.8 Hz 1H), 7.75-7.66 (m, 1H), 7.10 (dd, J=15.6, 9.0 Hz, 1H), 6.89 (d, J=15.9 Hz 1H), 4.86-4.80 (m, 1H); ESIMS m/z 441.1 ([M−H]⁻); IR (thin film) 3460, 2928, 1721, 1170, 764 cm⁻¹.

Example 20: Preparation of 5-Vinyl-2,3-dihydro-1H-inden-1-one (BI1)

To a stirred solution of 5-bromo-2,3-dihydro-1H-inden-1-one (5 g, 23.7 mmol) in toluene were added vinylboronic anhydride pyridine complex (8.55 g, 35.54 mmol), Pd(PPh₃)₄ (0.1 g, 0.094 mmol), K₂CO₃ (22.88 g, 165.83 mmol). The resultant reaction mixture was heated at reflux for 16 h. The reaction mixture was cooled to 25° C. and filtered, and the filtrate was concentrated under reduced pressure. The residue was diluted with EtOAc and washed with H₂O and brine. The combined organic extracts were dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The obtained residue was purified by flash column chromatography (SiO₂, 5% EtOAc in petroleum ether) afforded the title compound as a solid (1.8 g, 48%): ¹H NMR (400 MHz, CDCl₃) δ 7.74 (d, J=7.2 Hz, 1H), 7.49 (br s, 1H), 7.44 (d, J=7.2 Hz, 1H), 6.82 (m, 1H), 5.90 (d, J=7.4 Hz, 1H), 5.42 (d, J=6.4 Hz, 1H), 3.20 (m, 2H), 2.70 (m, 2H); ESIMS m/z 159.06 ([M+H]⁻).

The following compound was made in accordance with the procedures disclosed in Example 20.

6-Vinyl-3,4-dihydronaphthalen-1(2H)-one (BI2)

The product was isolated as an off-white solid (5 g, 48%): ¹H NMR (400 MHz, DMSO-d₆) δ 7.85 (d, J=8.4 Hz, 1H), 7.48 (m, 2H), 6.82 (m, 1H), 6.02 (d, J=7.4 Hz, 1H), 5.44 (d, J=6.4 Hz, 1H), 2.95 (m, 2H), 2.60 (m, 2H), 2.00 (m, 2H); ESIMS m/z 173.14 ([M−H]⁻); IR (thin film) 1681 cm⁻¹.

Example 21: Preparation of (E)-5-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1H-inden-1-one (BI3)

5-(1-Bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (4 g, 11.7 mmol), 5-vinyl-2,3-dihydro-1H-inden-1-one (0.92 g, 5.8 mmol), CuCl (0.115 g, 1.171 mmol) and 2,2-bipyridyl (0.053 g, 0.34 mmol) in 1,2-dichlorobenzene (25 mL) were heated at 180° C. for 16 h. The reaction mixture was cooled to 25° C. and concentrated under reduced pressure. The residue was purified by flash column chromatography (SiO₂, 5% EtOAc in petroleum ether) to afford the title compound as a liquid (1.28 g, 25%): ¹H NMR (400 MHz, CDCl₃) δ 7.76 (d, J=7.4 Hz, 1H), 7.52 (m, 3H), 6.68 (d, J=7.4 Hz, 1H), 6.52 (m, 1H), 4.18 (m, 1H), 3.18 (m, 2H), 2.75 (m, 2H); ESIMS m/z 419.14 ([M+H]⁻); IR (thin film) 1708.94, 1113.60, 807.77 cm⁻¹.

The following compound was made in accordance with the procedures disclosed in Example 21.

(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2,3-dihydro-1H-inden-1-one (BI4)

The product was isolated as a brown semi-solid (1.2 g, 16%): ¹H NMR (400 MHz, CDCl₃) δ 7.76 (d, J=7.4 Hz, 1H), 7.54 (m, 3H), 7.30 (s, 1H), 6.68 (d, J=7.4 Hz, 1H), 6.52 (m, 1H), 4.18 (m, 1H), 3.18 (m, 2H), 2.75 (m, 2H); ESIMS m/z 400.84 ([M−H]⁻); IR (thin film) 815, 1113, 1709 cm⁻¹.

(E)-6-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-3,4-dihydronaphthalen-1(21-1)-one (BI5)

The product was isolated as a pale yellow semi solid (1.2 g, 30%): ¹H NMR (400 MHz, CDCl₃) δ 8.20 (d, J=8.0 Hz, 1H), 7.42 (s, 2H), 7.35 (m, 1H), 7.24 (m, 2H), 6.62 (d, J=16 Hz, 1H), 6.46 (m, 1H), 4.18 (m, 1H), 2.95 (m, 2H), 2.65 (m, 2H), 2.19 (m, 2H); ESIMS m/z 432.94 ([M−H]⁻); IR (thin film) 1680, 1113, 808 cm⁻¹.

Example 22: Preparation of (E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-fluoro-2,3-dihydro-1H-inden-1-one (BI6)

To a stirred solution of (E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2,3-dihydro-1H-inden-1-one (0.5 g, 1.24 mmol) in acetonitrile (20 mL), was added Selectfluor® (0.52 g, 1.48 mmol) and the reaction was heated to reflux temperature for 16 h. The reaction mixture was cooled to room temperature, concentrated under reduced pressure and diluted with DCM. The solution was washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product which was purified by flash column chromatography (SiO₂, 100-200 mesh; 15% EtOAc in petroleum ether) to afford the title compound as a pale yellow semi solid (0.1 g, 24%): ¹H NMR (400 MHz, CDCl₃) δ 7.80 (m, 1H), 7.48 (m, 2H), 7.32 (m, 2H), 6.65 (d, J=16.0 Hz, 1H), 6.54 (dd, J=16.0, 8.0 Hz, 1H), 5.38 (m, 1H), 4.18 (m, 1H), 3.62 (m, 1H), 3.32 (m, 1H); ESIMS m/z 419.06 ([M−H]⁻); IR (thin film) 1728, 1114, 817 cm⁻¹.

Example 23: Preparation of (E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N-(3,3,3-trifluoropropyl)-2,3-dihydro-1H-inden-1-amine (BC10)

To a stirred solution of (E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2,3-dihydro-1H-inden-1-one (0.15 g, 0.35 mmol) in DCE (10 mL), was added trifluoropropyl amine (0.048 g, 0.42 mmol) and sodium cyanoborohydride (0.055 g, 0.875 mmol) in cooling and the reaction mixture was stirred at room temperature for 16 h. The reaction mixture was diluted with DCE, was washed with water and brine and dried over anhydrous sodium sulfate. Concentration under reduced pressure gave the crude compound, which was purified by flash column chromatography (SiO₂, 100-200 mesh; 10-15% EtOAc in petroleum ether) to afford the title compound as a colorless gummy material (0.042 g, 24%): ¹H NMR (400 MHz, CDCl₃) δ 7.38-7.20 (m, 5H), 6.62 (d, J=16.0 Hz, 1H), 6.34 (dd, J=16.0, 8.0 Hz, 1H), 5.83 (br, 1H), 5.52 (m, 1H), 4.12 (m, 1H), 3.02 (m, 3H), 2.82 (m, 1H), 2.50 (m, 2H), 1.82 (m, 1H), 1.42 (m, 1H); ESIMS m/z 497.98 ([M−H]⁻); IR (thin film) 3027, 1654, 815 cm⁻¹.

Example 24: Preparation of 6-((E)-4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-3,4-dihydronaphthalen-1(2H)-one oxime (BI5a)

To a stirred solution of ((E)-6-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-3,4-dihydronaphthalen-1(2H)-one (0.4 g, 0.92 mmol) in EtOH (50 mL) were added hydroxylamine hydrochloride (0.128 g, 1.85 mmol) and sodium acetate (0.23 g, 2.77 mmol), and the reaction mixture was heated at reflux for 3 h. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with H₂O and extracted with EtOAc. The combined organic extracts were washed with brine, dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to give the crude compound, which was purified by flash column chromatography (SiO₂, 100-200 mesh; 10-15% EtOAc in petroleum ether). The title compound was isolated as a solid (0.3 g, 73%): mp 155-158° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.89 (d, J=8.4 Hz, 1H), 7.41 (s, 2H), 7.24 (m, 1H), 7.17 (m, 1H), 6.57 (d, J=16 Hz, 1H), 6.46 (dd, J=16.0, 8.0 Hz, 1H), 4.13 (m, 1H), 2.82 (m, 4H), 2.04 (m, 2H); ESIMS m/z 445.95 ([M−H]⁻).

Example 25: Preparation of (E)-5-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1H-inden-1-amine (BI5b)

To a stirred solution of (E)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1H-inden-1-one (1 g, 2.39 mmol) in CH₃OH (10 mL) were added ammonium acetate (1.84 g, 23.9 mmol) and sodium cyanoborohydride (NaCNBH₃; 0.44 g, 7.17 mmol,) and the reaction mixture was heated at reflux for 16 h. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with H₂O and extracted with EtOAc. The combined organic extracts were washed with H₂O and saturated aqueous sodium bicarbonate (satd aq NaHCO₃) solution, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure to afford the title compound as a liquid (500 mg, crude): ¹H NMR (400 MHz, DMSO-d₆) δ 7.85 (s, 2H), 7.40 (s, 1H), 7.30 (s, 2H), 6.71 (s, 2H), 4.78 (m, 1H), 4.2 (m, 1H), 2.80 (m, 1H), 2.73 (m, 1H), 1.60 (m, 2H); ESIMS m/z 419.02 ([M+H]⁺); IR (thin film) 2924, 1552, 1112, 807 cm⁻¹.

The following compound was made in accordance with the procedures disclosed in Example 25.

(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2,3-dihydro-1H-inden-1-amine (BI7)

The product was isolated as a light brown gummy material, taken as such to the next step (0.15 g, crude compound): ESIMS m/z 401.97 ([M−H]⁻).

(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-fluoro-2,3-dihydro-1H-inden-1-amine (BI8)

The product was isolated as a light brown gummy material, taken as such to the next step (0.15 g, crude compound): ESIMS m/z 420.15 ([M−H]⁻).

(E)-6-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-1,2,3,4-tetrahydronaphthalen-1-amine (BI9)

The product was isolated as a pale yellow liquid (500 mg crude).

Example 26: Preparation of (E)-1-Methyl-3-(5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)-but-1-enyl)-2,3-dihydro-1H-inden-1-yl)thiourea (BC1)

To a stirred solution of (E)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1H-inden-1-amine (0.1 g, 0.23 mmol) in Et₂O (5 mL) was added methylisothiocyanate (0.026 g, 0.35 mmol), and the mixture was stirred for 2 h at 25° C. The reaction mixture was concentrated under reduced pressure, and the residue was purified by flash column chromatography (SiO₂, 20% EtOAc in petroleum ether). The title compound was isolated as a liquid (65 mg, 50%): ¹H NMR (400 MHz, CDCl₃) δ 7.39 (s, 2H), 7.25-7.18 (m, 3H), 6.58 (d, J=16.0 Hz, 1H), 6.30 (dd, J=16.0, 8.4 Hz, 1H), 5.91-5.70 (br, 2H), 4.05 (m, 1H), 3.05-2.80 (m, 6H), 2.70 (m, 1H), 1.81 (m, 1H); ESIMS m/z 492.17 ([M+H]⁺); IR (thin film) 3211, 1569, 1113, 806 cm⁻¹.

Compounds BC2-BC3 in Table 1 were made in accordance with the procedures disclosed in Example 26.

Example 27: Preparation of (E)-3,3,3-Trifluoro-N-(5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1H-inden-1-yl)propanamide (BC4)

To a stirred solution of (E)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1H-inden-1-amine (0.1 g, 0.23 mmol) in CH₂Cl₂ (10 mL) were added trifluoropropionic acid (0.044 g, 0.34 mmol), EDC.HCl (0.038 g, 0.35 mmol), HOBt.H₂O (0.07 g, 0.46 mmol) and DIEA (0.074 g, 0.57 mmol), and the reaction mixture was stirred for 16 h at 25° C. The reaction mixture was diluted with CH₂Cl₂ and washed with H₂O. The combined organic layer was washed with brine, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. The crude material was purified by flash column chromatography (SiO₂, 15% EtOAc in petroleum ether) to afford the title compound as a liquid (65 mg, 65%): ¹H NMR (400 MHz, CDCl₃) δ 7.39 (s, 2H), 7.25-7.20 (m, 3H), 6.34 (d, J=16.0 Hz, 1H), 6.30 (dd, J=16.0, 8.0 Hz, 1H), 5.81 (br, 1H), 5.48 (m, 1H), 4.10 (m, 1H), 3.10 (m, 2H), 2.86-3.07 (m, 2H), 2.86 (m, 1H), 1.81 (m, 1H); ESIMS m/z 529.02 ([M+H]⁺); IR (thin film) 3283, 1652, 1241, 811 cm⁻¹.

Compounds BC5-BC9, BC11 in Table 1 were made in accordance with the procedures disclosed in Example 27.

Example 28: Preparation of tert-Butyl 5-vinylindoline-1-carboxylate (BI10)

Step 1. 5-Bromo-indoline (BI11)

To 5-Bromo-1H-indole (2.5 g, 12.82 mmol) in acetic acid (10.0 mL), NaCNBH₃ (2.38 g, 38.46 mmol) was added portion wise at 10° C. over the period of 20 min. After that the reaction mixture was stirred at RT for 3 h. The reaction mixture was diluted with water and extracted with diethyl ether. The organic layer was washed with saturated NaHCO₃, water and brine solution. The combined ether layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford title compound as a pale yellow semi-solid (1.8 g, 71%).

Step 2. tert-Butyl-5-bromoindoline-1-carboxylate (BI12)

To a stirred solution of 5-bromo-indoline (3.0 g, 15 mmol) in acetonitrile (100 ml), was added DMAP (0.185 g, 1.522 mmol) and di-tert-butyl dicarbonate (3.98 g, 18.3 mmol) and the reaction was stirred at RT for 16 h. The reaction mixture was concentrated on reduced pressure to obtain a residue which was diluted with diethyl ether and washed with water and brine solution (2×). The combined ether layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude product as an off-white solid, which was used in the next step without further purification (3.0 g).

Step 3. tert-Butyl-5-vinylindoline-1-carboxylate (BI10)

A stirred solution of tert-butyl-5-bromoindoline-1-carboxylate (2.0 g, 6.73 mmol), potassium vinyl trifluoroborate (2.6 g, 20.20 mmol) and K₂CO₃ (2.78 g, 20.2 mmol) in DMSO (50.0 mL) was degassed with argon for 20 min at RT. PdCl₂(dppf) (0.49 g, 0.67 mmol) was added at RT, then the reaction mixture was heated to 100° C. for 3 h. The reaction mixture was cooled to RT and filtered through a celite bed under vacuum and washed with diethyl ether. The reaction mixture was extracted with diethyl ether. The combined diethyl ether layer was dried over Na₂SO₄ and concentrated under reduced pressure to afford crude product. The crude compound was purified by column chromatography (SiO₂, 100-200 mesh; eluting with 2% ethyl acetate/petroleum ether) to afford the title compound as an off-white solid (1.2 g, 73%): Mp 85.5-88.6° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.23 (m, 3H), 6.69 (dd, J=17.4, 10.8 Hz, 1H), 5.64 (d, J=10.5 Hz, 1H), 5.13 (d, J=10.5 Hz, 1H), 4.00 (t, J=9.0 Hz, 2H), 3.10 (t, J=9.0 Hz, 2H), 1.55 (bs, 9H).

Example 29: Preparation of (E)-tert-Butyl 5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)indoline-1-carboxylate (BI13)

To a stirred solution of tert-butyl-5-vinylindoline-1-carboxylate (1.28 g, 5.23 mmol) in 1,2-dichlorobenzene (10.0 mL), was added 5-(1-bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-fluorobenzene (3.4 g, 10 mmol), CuCl (103 mg, 1.05 mmol) and 2,2-bipyridyl (0.326 g, 2.092 mmol) and the resultant reaction mixture was degassed with argon for 30 min and heated to 150° C. for 1 h. The reaction mixture was cooled to RT and filtered and the filtrate was concentrated under reduced pressure. The crude compound was purified by column chromatography (SiO₂, 100-200 mesh; 2% ethyl acetate/petroleum ether) to afford the title compound as a pale yellow gummy solid (0.3 g, 61%): ¹H NMR (400 MHz, CDCl₃) δ 7.34 (d, J=6.0 Hz, 2H), 7.22 (s, 2H), 7.16 (d, J=8.4 Hz, 1H), 6.52 (d, J=16.0 Hz, 1H), 6.21 (dd, J=16.0, 7.6 Hz, 1H), 4.07 (m, 3H), 3.10 (t, J=8.4 Hz, 2H), 1.55 (s, 9H); ESIMS m/z 433.79 ([M−H]⁻); IR (thin film) 1168, 858 cm⁻¹.

Example 30: Preparation of (E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)indolin-1-amine (BI14)

Step 1. (E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)indoline (BI15)

To a stirred solution of (E)-tert-butyl-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)indoline-1-carboxylate (0.2 g, 0.4 mmol) in DCM (10.0 mL) was added TFA (0.6 mL) and the reaction was stirred at RT for 2 h. The reaction mixture was diluted with DCM, washed with saturated aq NaHCO₃, water and brine solution. The separated DCM layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude product as a light brown gummy material which was used in the next step without further purification (0.12 g): ¹H NMR (400 MHz, CDCl₃) δ 7.33 (d, J=6.4 Hz, 2H), 7.21 (s, 1H), 7.02 (d, J=8.0 Hz, 1H), 6.57 (d, J=8.4 Hz, 1H), 6.49 (d, J=15.6 Hz, 1H), 6.21 (dd, J=15.6, 8.4 Hz, 1H), 4.07 (m, 1H), 3.61 (t, J=8.4 Hz, 2H), 3.05 (t, J=8.4 Hz, 2H); ESIMS m/z 389.89 ([M+H]⁺); IR (thin film) 3385, 1112, 816 cm⁻¹.

Step 2. 5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1-nitrosoindoline (BI16)

To (E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)indoline (0.2 g, 0.5 mmol) in concentrated HCl (5.0 ml) at 5° C., was added slowly NaNO₂ in water and the reaction was allowed to stir at RT for 2 h. The reaction mixture was diluted with DCM, and the DCM layer washed with water and brine solution. The separated DCM layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude product as a pale yellow solid that was used in the next step without further purification (0.2 g): ¹H NMR (400 MHz, CDCl₃) δ 7.33 (d, J=8.4 Hz, 1H), 7.39 (m, 4H), 6.61 (d, J=16.0 Hz, 1H), 6.35 (dd, J=16.0, 8.4 Hz, 1H), 4.07 (m, 3H), 3.23 (t, J=8.4 Hz, 2H); ESIMS m/z 418.82 ([M+H]⁺); IR (thin film) 1488, 1112, 860 cm⁻¹.

Step 3. (E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)indolin-1-amine (BI14)

To (E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1-nitrosoindoline (0.1 g, 0.2 mmol) in methanol (10.0 mL) was added zinc powder (77.5 mg) and NH₄Cl (36.9 mg, 0.69 mmol) in water (2.0 mL). The reaction mixture was stirred at RT for 3 h. The reaction mixture was diluted with DCM and the DCM layer was washed with water and brine solution. The separated DCM layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude compound, which was purified by column chromatography (SiO₂, 100-200 mesh; eluting with 2% ethyl acetate/petroleum ether) to afford the title compound as a light brown gummy material (0.08 g): ESIMS m/z 404.86 ([M+H]⁺).

Example 31: Preparation of (E)-N-(5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)indolin-1-yl)-3,3,3-trifluoropropanamide (BC12)

To a stirred solution of (E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)indoline-1-amine (0.1 g, 0.247 mmol) in DCM (10.0 ml) was added 3,3,3-trifluoropropanoic acid (0.038 g, 0.297 mmol), PyBOP (0.192 g, 0.370 mmol) and DIEA (0.047 g, 0.370 mmol) and the reaction was stirred at RT for 18 h. The reaction mixture was diluted with DCM, and the separated DCM layer dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column chromatography (SiO₂, 100-200 mesh; 20-25% ethyl acetate/petroleum ether) to afford the title compound as a light brown gummy material (0.12 g, 33%): ¹H NMR (400 MHz, CDCl₃) δ 7.32, (d, J=6.0 Hz, 2H) 7.28 (m, 1H), 7.20 (d, J=8.0, 1H), 7.14 (d, J=8.8, 1H), 6.70 (d, J=8.0 Hz, 1H), 6.60 (m, 2H), 4.15 (m, 1H), 3.85 (m, 1H), 3.65 (m, 1H), 3.46 (m, 2H), 3.19 (m, 2H); ESIMS m/z 514.86 ([M+H]⁺); IR (thin film) 3428, 1112, 857 cm⁻¹.

Example 32: Preparation of tert-Butyl-5-vinyl-1H-indole-1-carboxylate (BI17)

Step 1. 5-Vinyl-1H-indole (BI18)

A mixture of 5-bromo-1H-indole (2.5 g, 12.82 mmol), potassium vinyltrifluoroborate (2.57 g, 19.2 mmol), Cs₂CO₃ (12.53 g, 38.46 mmol) and triphenylphosphine (201 mg, 0.769 mmol) in THF/water (9:1, 75 ml) was degassed with argon for 20 min, then charged with PdCl₂ (45.3 mg, 0.256 mmol). The reaction mixture was heated to reflux for 16 h, then cooled to RT, filtered through celite bed and washed with ethyl acetate. The filtrate was again extracted with ethyl acetate, and the combined organic layer washed with water and brine, dried over Na₂SO₄ and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column chromatography (SiO₂, 100-200 mesh; 2% ethyl acetate/petroleum ether) to afford the title compound as a light brown gummy material (1.5 g, 83%): ¹H NMR (400 MHz, CDCl₃) δ 8.20 (br, 1H), 7.68 (s, 1H), 7.45 (s, 2H), 7.21 (m, 1H), 6.90 (dd, J=16.0, 10.8 Hz, 1H), 6.55 (m, 1H), 5.75 (d, J=10.5 Hz, 1H), 5.21 (d, J=10.5 Hz, 1H); ESIMS m/z 142.05 ([M−H]⁻).

Step 2. tert-Butyl-5-vinyl-1H-indole-1-carboxylate (BI17)

To a stirred solution of 5-vinyl-1H-indole (0.7 g, 4.89 mmol) in acetonitrile (20 ml) was added DMAP (59.65 mg, 0.489 mmol) and di-tert-butyl dicarbonate (1.38 g, 6.36 mmol), and the reaction was stirred at RT for 3 h. The reaction mixture was concentrated under reduced pressure to obtain a residue which was diluted with DCM and washed with water and brine solution. The combined DCM layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column chromatography (SiO₂, 100-200 mesh; 2% ethyl acetate/petroleum ether) to afford the title compound as an off-white semi-solid (0.7 g, 59%): ¹H NMR (400 MHz, CDCl₃) δ 8.15 (d, J=8.0 Hz, 1H), 7.60 (s, 2H), 7.30 (d, J=8.4 Hz, 1H), 7.21 (m, 1H), 6.90 (dd, J=16.0, 10.8 Hz, 1H), 6.59 (s, 1H), 5.75 (d, J=10.5 Hz, 1H), 5.21 (d, J=10.5 Hz, 1H), 1.65 (s, 9H); ESIMS m/z 242.10 ([M−H]⁻); IR (thin film) 1630 cm⁻¹.

Example 33: Preparation of (E)-tert-Butyl 5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1H-indole-1-carboxylate (BI19)

To a stirred solution of tert-butyl 5-vinyl-1H-indole-1-carboxylate (0.65 g, 2.67 mmol), in 1,2-dichlorobenzene (10.0 mL) was added 5-(1-bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-fluorobenzene (1.74 g, 5.37 mmol), CuCl (53 mg, 0.537 mmol) and 2,2-bipyridyl (167 mg, 1.07 mmol). The resultant reaction mixture was degassed with argon for 30 min and heated to 150° C. for 2 h. The reaction mixture was cooled to RT and filtered, and the filtrate concentrated under reduced pressure. The crude compound was purified by column chromatography (SiO₂, 100-200 mesh; 2% ethyl acetate/petroleum ether) to afford the title compound as a light brown gummy material (0.25 g, 10%): ¹H NMR (400 MHz, CDCl₃) δ 8.20 (d, J=8.0 Hz, 1H), 7.60 (m, 2H), 7.39 (m, 3H), 6.69 (d, J=16.0 Hz, 1H), 6.55 (d, J=10.5 Hz, 1H), 6.36 (dd, J=16.0, 8.0 Hz, 1H), 4.10 (m, 1H), 1.65 (s, 9H); ESIMS m/z 485.91 ([M−H]⁻); IR (thin film) 1165, 854 cm⁻¹.

Example 34: Preparation of (E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1H-indole (BI20)

To a stirred solution of (E)-tert-butyl 5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1H-indole-1-carboxylate (0.2 g, 0.40 mmol) in DCM (10.0 mL) was added TFA (70 mg, 0.61 mmol) and the reaction was stirred at RT for 2 h. The reaction mixture was diluted with DCM and washed with saturated NaHCO₃ solution, water and brine solution. The separated DCM layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the title compound as a light brown solid (0.2 g, 97%): mp 132.9-138.8° C.; ¹H NMR (400 MHz, CDCl₃) δ 11.19 (br, 1H), 8.20 (d, J=8.0 Hz, 1H), 7.60 (m, 2H), 7.39 (m, 3H), 6.69 (d, J=16.0 Hz, 1H), 6.55 (d, J=10.5 Hz, 1H), 6.36 (dd, J=16.0, 8.0 Hz, 1H), 4.82 (m, 1H); ESIMS m/z 387.98 ([M+H]⁺).

Example 35: Preparation of 4-Nitrophenyl 2-((tert-butoxycarbonyl)amino)acetate (BI21)

To a stirred solution of 4-nitrophenol (1.0 g, 7.19 mmol) in DCM (20.0 mL) was added N-Boc glycine (1.38 g, 7.91 mmol) and EDC HCl (2.05 g, 10.785 mmol) and the reaction was stirred at RT for 24 h. The reaction mixture was diluted with DCM and washed with water and saturated brine solution. The separated DCM layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the title compound as a light brown gummy material that was used in the next step without further purification (1.1 g): ¹H NMR (400 MHz, CDCl₃) δ 8.29 (d, J=9.2 Hz, 2H), 7.33 (d, J=8.8 Hz, 2H), 5.07 (br, 1H), 4.20 (s, 2H), 1.47 (s, 9H); ESIMS m/z 296.27 ([M+H]⁺).

Example 36: Preparation of (E)-tert-Butyl (2-(5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1H-indol-1-yl)-2-oxoethyl)carbamate (BI22)

To a stirred solution of (E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1H-indole (0.1 g, 0.258 mmol) in acetonitrile (5.0 mL) was added 4-nitrophenyl 2-(tert-butoxycarbonylamino) acetate (0.114 g, 0.387 mmol), potassium fluoride (0.03 g, 0.516 mmol), 18-crown-6-ether (0.075 g, 0.283 mmol) and DIEA (0.0332 g, 0.258 mmol) and the reaction was stirred at RT for 16 h. The reaction mixture was concentrated to obtain a residue which was diluted with DCM and washed with water and brine solution. The separated DCM layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude title compound as a light brown gummy material which was used in the next step without further purification (0.1 g): ESIMS m/z 545.23 ([M+H]⁺).

Example 37: Preparation of (E)-N-(2-(5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1H-indol-1-yl)-2-oxoethyl)-3,3,3-trifluoropropanamide (BC13)

Step 1. (E)-2-amino-1-(5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1H-indol-1-yl)ethanone (BI23)

To a stirred solution of (E)-tert-butyl 2-(5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1H-indol-1-yl)-2-oxoethylcarbamate (0.05 g, 0.09 mmol) in DCM (5.0 mL) was added TFA (0.01 mL) and the reaction was stirred at RT for 16 h. The reaction mixture was diluted with DCM and washed with saturated NaHCO₃ solution, water and brine solution. The separated DCM layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude title compound which was used in the next step without further purification (50 mg).

Step 2. (E)-N-(2-(5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1H-indol-1-yl)-2-oxoethyl)-3,3,3-trifluoropropanamide (BC13)

To a stirred solution of (E)-2-amino-1-(5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1H-indol-1-yl) ethanone (0.04 g, 0.09 mmol) in DCM (5.0 ml) was added 3,3,3-trifluoropropanoic acid (17.5 mg, 0.136 mmol), PyBOP (70 mg, 0.135 mmol) and DIEA (29 mg, 0.225 mmol) and the reaction was stirred at RT for 16 h. The reaction mixture was diluted with DCM, and the DCM layer was washed with water and saturated brine solution. The separated DCM layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude compound, which was purified by column chromatography (SiO₂, 100-200 mesh; 10% ethyl acetate/petroleum ether) to afford the title compound as an off-white solid (30 mg, 60%): mp 121-126° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.33 (br, 1H), 7.59 (s, 1H), 7.45 (m, 4H), 6.72 (d, J=3.6 Hz, 3H), 6.39 (m, 1H), 4.71 (t, J=7.2 Hz, 2H), 4.15 (m, 1H), 3.51 (m, 1H), 3.28 (m, 1H); ESIMS m/z 553.06 ([M−H]⁻).

Example 38: Preparation of Ethyl 2-(1-oxo-6-vinylphthalazin-2(1H)-yl)acetate (BI24)

Step 1. 5-Bromo-3-hydroxyisoindoline-1-one (BI25)

A mixture of Zn powder (1.73 g, 26.154 mmol), copper (II) sulfate pentahydrate (0.02 g, 0.08 mmol) and 2M aq NaOH (27 mL) were cooled to 0° C. 5-Bromoisoindoline-1,3-dione (5 g, 22 mmol) was added at the same temperature over the period of 30 min. The reaction mixture was stirred at 0° C. for 30 min and 3 h at RT. The reaction mixture was filtered and the filtrate was neutralized with concentrated HCl. The reaction mixture was diluted with ethanol and extracted with ethyl acetate. The combined ethyl acetate layer was dried over Na₂SO₄ and concentrated under reduced pressure to afford the crude title compound as a brown solid, which was used in the next step without further purification (1.3 g): mp 258-261° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 9.03 (br, 1H), 7.81 (m, 2H), 7.69 (m, 1H), 6.44 (m, 1H), 5.88 (d, J=9.3 Hz, 1H); ESIMS m/z 225.83 ([M−H]⁻); IR (thin film) 1684, 3246, 606 cm⁻¹.

Step 2. 6-Bromophthalazine-1(2H)-one (BI26)

To a stirred solution of 5-bromo-3-hydroxyisoindoline-1-one (1.0 g, 4.40 mmol) in water, was added hydrazine hydrate (0.45 g, 8.80 mmol) and heated to 95° C. for 5 h. The reaction mixture was cooled to RT, filtered and washed with diethyl ether and pentane (1:1) to afford the title compound as a white solid that was used in the next step without further purification (0.5 g): ESIMS m/z 225.15 ([M+H]⁺).

Step 3. 6-Vinylphthalazine-1(2H)-one (BI27)

A solution of 6-bromophthalazine-1(2H)-one (0.25 g, 1.11 mmol), potassium vinyl trifluoroborate (0.446 g, 3.33 mmol) and K₂CO₃ (0.46 g, 3.33 mmol) in DMSO (2 mL) was degassed with argon for 20 min at RT. PdCl₂(dppf) (0.04 g, 0.055 mmol) was added at RT, and the reaction mixture was heated to 80° C. for 2 h. The reaction mixture was cooled to RT and filtered through celite bed under vacuum and washed with ethyl acetate. The reaction mixture was extracted with ethyl acetate and the combined ethyl acetate layer dried over Na₂SO₄ and concentrated under reduced pressure to afford the crude product. The crude compound was purified by column chromatography (SiO₂, 100-200 mesh; 50% ethyl acetate/petroleum ether) to afford the title compound as a brown solid (0.12 g, 63%): ¹H NMR (400 MHz, DMSO-d₆) δ 13.61 (br, 1H), 8.33 (m, 1H), 8.19 (m, 1H), 8.01 (m, 2H), 6.97 (m, 1H), 6.15 (m, 1H), 5.56 (d, J=10.8 Hz, 1H); ESIMS m/z 172.93 ([M+H]⁺); IR (thin film) 1748, 1655, 3241 cm⁻¹.

Step 4. Ethyl-2-(1-oxo-6-vinylphthalazine-2(1H)-yl acetate (BI24)

To a stirred solution of 6-vinylphthalazine-1(2H)-one (0.5 g, 2.90 mmol) in DMF (5.0 mL) was added Cs₂CO₃ (0.94 g, 2.90 mmol) and the reaction was stirred for 10 min. Ethyl bromoacetate (0.48 g, 2.90 mmol) was added to the reaction mixture at RT and the reaction was stirred for 8 h at RT. The reaction mixture was diluted and extracted with ethyl acetate, and the ethyl acetate layer was washed with water and brine solution (2×). The separated ethyl acetate layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford crude product. The crude compound was purified by column chromatography (SiO₂, 100-200 mesh; 25% ethyl acetate/petroleum ether) to afford the title compound as a brown solid (0.34 g, 45%): ¹H NMR (400 MHz, DMSO-d₆) δ 8.45 (m, 1H), 8.24 (m, 1H), 8.04 (m, 2H), 7.01 (m, 1H), 6.17 (d, J=2.1 Hz, 1H), 5.56 (d, J=10.8 Hz, 1H), 4.92 (s, 2H), 4.19 (m, 2H), 1.23 (m, 3H). ESIMS m/z 259.10 ([M+H]⁺); IR (thin film) 1750, 1660 cm⁻¹.

Example 39: Preparation of (E)-Ethyl 2-(6-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1-oxophthalazin-2(1H)-yl)acetate (BI28)

To a stirred solution of ethyl-2-(1-oxo-6-vinylphthalazine-2(1H)-yl acetate (0.07 g, 0.27 mmol) in 1,2-dichlorobenzene (1.0 mL) was added 5-(1-bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2fluorobenzene (0.17 g, 0.54 mmol), CuCl (0.005 g, 0.05 mmol) and 2,2-bipyridyl (0.016 g, 0.10 mmol) and the resultant reaction mixture was degassed with argon for 30 min and heated to 180° C. for 12 h. The reaction mixture was cooled to RT and filtered and the filtrated was concentrated under reduced pressure. The crude compound was purified by column chromatography (SiO₂, 100-200 mesh; 10-15% ethyl acetate/petroleum ether) to afford the title compound as a brown solid (40 mg, 29%): ¹H NMR (400 MHz, DMSO-d₆) δ 8.40 (d, J=8.4 Hz, 1H), 7.84 (d, J=1.5 Hz, 1H), 7.65 (s, 1H), 7.37 (d, J=6.3 Hz, 2H), 6.76 (d, J=16.0 Hz, 1H), 6.59 (dd, J=16.0, 8.0 Hz, 1H), 4.96 (s, 2H), 4.29 (m, 3H), 1.31 (t, J=7.2 Hz, 3H); ESIMS m/z 503.0 ([M+H]⁺); IR (thin film) 1660, 1114, 817 cm⁻¹.

Example 40: Preparation of (E)-2-(6-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1-oxophthalazin-2(1H)-yl)acetic acid (BI29)

A solution of (E)-ethyl-2-(6-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1-oxophthalazin-2(1H)-yl) acetate (0.04 g, 0.07 mmol) in HCl (0.5 mL) and acetic acid (0.5 mL) was heated to 100° C. for 3 h. The solvent was removed under reduced pressure and the residue diluted with water. The aqueous layer was extracted with ethyl acetate and the separated ethyl acetate layer dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude compound. The crude compound was triturated with diethyl ether-pentane mixture to afford the title compound as a brown solid (0.03 g): ¹H NMR (400 MHz, DMSO-d₆) δ 13.0 (br s, 1H), 8.43 (m, 1H), 8.23 (d, J=8.1 Hz, 1H), 8.14 (m, 2H), 7.91 (m, 2H), 7.16 (dd, J=16.0, 8.0 Hz, 1H), 6.99 (d, J=16.0 Hz, 1H), 4.96 (m, 3H); ESIMS m/z 473.0 ([M−H]⁻); IR (thin film) 1629, 1168, 817 cm⁻¹.

Example 41: Preparation of (E)-2-(6-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-1-oxophthalazin-2(1H)-yl)-N-(2,2,2-trifluoroethyl)acetamide (BC14)

To a stirred solution of (E)-2-(6-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-1-oxophthalazin-2(1H)-yl)acetic acid (0.15 g, 0.31 mmol) in DCM (20.0 ml) was added 2,2,2,-trifluoroethanamine (0.03 g, 0.31 mmol), PyBOP (0.17 g, 0.34 mmol) and DIEA (0.15 ml, 0.93 mmol) at RT, and the reaction was stirred for 18 h. The reaction mixture was diluted with DCM and washed with 3N HCl (2×20 mL), NaHCO₃ (2×20 mL) and brine solution (2×). The separated DCM layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column chromatography (SiO₂, 100-200 mesh; 20-25% ethyl acetate/petroleum ether) to afford the title compound as a brown solid (0.11 g): mp 172-175° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.83 (t, J=6.6 Hz, 1H), 8.42 (t, J=14.7 Hz, 1H), 8.22 (d, J=8.1 Hz, 1H), 8.13 (t, J=6.3 Hz, 1H), 7.98-7.86 (m, 2H), 7.16-7.07 (m, 1H), 7.01-6.93 (m, 1H), 4.96-4.81 (m, 3H), 4.00-3.88 (m, 2H); ESIMS m/z 554.0 ([M−H]⁻).

Example 42: Preparation of 2-(4-Vinylbenzyl)isoindoline-1,3-dione (CI1)

To a stirred solution of 1-(chloromethyl)-4-vinylbenzene (10 g, 66 mmol) in DMF (100 mL) was added potassium phthalimide (13.3 g, 72.1 mmol), and the resultant reaction mixture was heated at 70° C. for 16 h. The reaction mixture was diluted with H₂O and extracted with CHCl₃. The combined CHCl₃ layer was washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure. Recrystallization from CH₃OH afforded the title compound as an off-white solid (8 g, 46%): ¹H NMR (400 MHz, CDCl₃) δ 7.83 (m, 2H), 7.71 (m, 2H), 7.39 (m, 4H), 6.65 (dd, J=17.6, 10.8 Hz, 1H), 5.72 (d, J=17.6 Hz, 1H), 5.21 (d, J=10.8 Hz, 1H), 4.82 (s, 2H); GCMS m/z 263.2 ([M]⁺); IR (thin film) 3420, 1133, 718 cm⁻¹.

Example 43: Preparation of (E)-2-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)isoindoline-1,3-dione (CI2)

Using the procedure of Example 10 with 2-(4-vinylbenzyl)isoindoline-1,3-dione and 1-(1-bromoethyl)-3,5-dichlorobenzene as the starting materials, the title compound was isolated as an off-white solid (0.3 g, 40-50%): mp 142-145° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.86 (m, 2H), 7.74 (m, 2H), 7.42 (m, 2H), 7.36 (m, 3H), 7.27 (m, 2H), 6.58 (d, J=16.0 Hz, 1H), 6.32 (dd, J=16.0, 8.0 Hz, 1H), 4.82 (s, 2H), 4.05 (m, 1H); ESIMS m/z 488.17 ([M−H]⁻).

The following compound was made in accordance with the procedures disclosed in Example 43.

(E)-2-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)isoindoline-1,3-dione (CI3)

The title compound was isolated as an off white solid (0.3 g, 56%): mp 145-146° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.86 (m, 2H), 7.74 (m, 2H), 7.42-7.31 (m, 6H), 6.58 (d, J=16.0 Hz, 1H), 6.53 (dd, J=16.0, 8.0 Hz, 1H), 4.82 (s, 2H), 4.05 (m, 1H); ESIMS m/z 522.2 ([M−H]⁻); IR (thin film) 1716, 1110, 712 cm⁻¹.

Prophetically, compounds CI4-CI5 (Table 1) could be made in accordance with the procedures disclosed in Example 43.

Example 44: Preparation of (E)-(4-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine (CI6)

To a stirred solution of (E)-2-(4-(3-(3,5-dichlorophenyl)but-1-en-1-yl)benzyl)-isoindoline-1,3-dione (1.2 g, 2.45 mmol) in EtOH was added hydrazine hydrate (0.61 g, 12 mmol), and the resultant reaction mixture was heated at 90° C. for 1 h. The reaction mixture was filtered, and the filtrate was concentrated. The residue was dissolved in CH₂Cl₂, washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure to afford the crude title compound as a gummy liquid (0.9 g) which was used without further purification.

The following compounds were made in accordance with the procedures disclosed in Example 44.

(E)-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)methanamine (CI7)

The title compound was isolated and used without further purification.

Prophetically, compounds CI8-CI9 (Table 1) could be made in accordance with the procedures disclosed in Example 44.

Example 45: Preparation of 4-(Bromomethyl)-3-chlorobenzonitrile (CI10)

To a stirred solution of 3-chloro-4-methylbenzonitrile (5 g, 25.4 mmol) in carbon tetrachloride (CCl₄; 50 mL) under an argon atmosphere was added NBS (5.16 g, 29 mmol), and the mixture was degassed for 30 min. To this was added azobisisobutyronitrile (AIBN; 0.3 g, 1.8 mmol), and the resultant reaction mixture was heated at reflux for 4 h. The reaction mixture was cooled to ambient temperature, washed with H₂O, and extracted with CH₂Cl₂. The combined CH₂Cl₂ layer was washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure. The crude compound was purified by flash column chromatography (SiO₂, 100-200 mesh; 5% EtOAc in n-Hexane) to afford the title compound as a white solid (4.8 g, 68%): mp 87-88° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.71 (s, 1H), 7.59 (s, 2H), 4.60 (s, 2H); ESIMS m/z 229.77 ([M+H]⁺); IR (thin film) 2235, 752, 621 cm⁻¹.

The following compounds were made in accordance with the procedures disclosed in Example 45.

4-(Bromomethyl)-3-(trifluoromethyl)benzonitrile (CI11)

The title compound was isolated as an off-white gummy material (5 g, 66%): ¹H NMR (400 MHz, CDCl₃) δ 7.96 (s, 1H), 7.86 (d, J=8.0 Hz, 1H), 7.76 (d, J=8.0 Hz, 1H), 4.62 (s, 2H); ESIMS m/z 262.11 ([M−H]⁻); IR (thin film) 2236, 1132, 617 cm⁻¹.

3-Bromo-4-(bromomethyl)benzonitrile (CI12)

The title compound was isolated as an off-white solid (5 g, 67%): mp 82-83° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.90 (s, 1H), 7.61 (m, 2H), 4.62 (s, 2H); EIMS m/z 272.90; IR (thin film) 2229, 618 cm⁻¹.

4-(Bromomethyl)-3-fluorobenzonitrile (CI13)

The title compound was isolated as an off-white solid (2 g, 60%): mp 79-81° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.54 (t, J=8.0 Hz, 1H), 7.48 (dd, J=8.0 Hz, 8.0, 1H), 7.38 (dd, J=5 Hz, 1H), 4.5 (s, 2H); EIMS m/z 215.

Example 46: Preparation of 4-(Bromomethyl)-3-chlorobenzaldehyde (CI14)

To a stirred solution of 4-(bromomethyl)-3-chlorobenzonitrile (4.8 g, 17 mmol) in toluene (50 mL) at 0° C. was added dropwise diisobutylaluminum hydride (DIBAL-H, 1.0 M solution in toluene; 23.9 mL), and the reaction mixture was stirred at 0° C. for 1 h. 10 M HCl in H₂O (5 mL) was added until the reaction mixture turned to a white slurry and then additional 1 N HCl (20 mL) was added. The organic layer was collected and the aqueous layer was extracted with CHCl₃. The combined organic layer was dried over Na₂SO₄ and concentrated under reduced pressure. The crude compound was purified by flash column chromatography (SiO₂, 100-200 mesh; 5% EtOAc in n-Hexane) to afford the title compound as a white solid (3.8 g, 80%): mp 64-66° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.00 (s, 1H), 7.92 (s, 1H), 7.78 (d, J=8.0 Hz, 1H), 7.64 (d, J=8.0 Hz, 1H), 4.60 (s, 2H); ESIMS m/z 232.78 ([M+H]⁺).

The following compounds were made in accordance with the procedures disclosed in Example 46.

4-(Bromomethyl)-3-(trifluoromethyl)benzaldehyde (CI15)

The title compound was isolated as a pale yellow low-melting solid (5 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 10.09 (s, 1H), 8.19 (s, 1H), 8.09 (m, 1H), 7.81 (m, 1H), 4.61 (s, 2H); ESIMS m/z 265.04 ([M−H]⁻); IR (thin film) 1709, 1126, 649 cm⁻¹.

3-Bromo-4-(bromomethyl)benzaldehyde (CI16)

The title compound was isolated as a pale yellow solid (5 g, 62%): mp 94-95° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.96 (s, 1H), 8.05 (s, 1H), 7.81 (d, J=8.0 Hz, 1H), 7.62 (d, J=8.0 Hz, 1H), 4.60 (s, 2H); EIMS m/z 275.90.

4-(Bromomethyl)-3-fluorobenzaldehyde (CI17)

The title compound was isolated as an off-white solid (5 g, 61%): mp 43-45° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.1 (s, 1H), 7.54 (t, J=8 Hz, 1H), 7.48 (d, J=8 Hz, 1H), 7.38 (d, J=5 Hz, 1H), 4.5 (s, 2H); EIMS m/z 216.

Example 47: Preparation of 3-Chloro-4-((1,3-dioxoisoindolin-2-yl)methyl)benzaldehyde (CI18)

To a stirred solution of 4-(bromomethyl)-3-chlorobenzaldehyde (3.8 g, 14 mmol) in DMF (40 mL) was added potassium pthalimide (3.54 g, 19.14 mmol), and the mixture was heated at 60° C. for 6 h. The reaction mixture was cooled to ambient temperature and diluted with H₂O (100 mL). The solid obtained was separated by filtration and dried under vacuum to afford the title compound as a white solid (2.8 g, 60%): mp 123-126° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.95 (s, 1H), 8.21 (s, 1H), 7.91 (m, 3H), 7.80 (m, 2H), 7.20 (m, 1H), 5.05 (s, 2H); ESIMS m/z 298.03 ([M−H]⁻).

The following compounds were made in accordance with the procedures disclosed in Example 47.

4-((1,3-Dioxoisoindolin-2-yl)-3-(trifluoromethyl)benzaldehyde (CI19)

The title compound was isolated as an off white solid (1 g, 62%): mp 142-143° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.05 (s, 1H), 8.15 (s, 1H), 7.91 (m, 2H), 7.80 (m, 3H), 7.27 (m, 1H), 5.19 (s, 2H); ESIMS m/z 332.03 ([M−H]⁻).

3-Bromo-4-((1,3-dioxoisoindolin-2-yl)methyl)benzaldehyde (CI20)

The title compound was isolated as an off-white solid (0.5 g, 64%): mp 159-161° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.95 (s, 1H), 8.21 (s, 1H), 7.91 (m, 3H), 7.80 (m, 2H), 7.20 (m, 1H), 5.05 (s, 2H); ESIMS m/z 314.00 ([M-CHO]⁻).

4-((1,3-Dioxoisoindolin-2-yl)-3-fluorobenzaldehyde (CI21)

The title compound was isolated as a white solid (2 g, 60%): mp 154-156° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.95 (s, 1H), 7.9 (m, 2H), 7.75 (m, 2H), 7.6 (m, 2H), 7.5 (t, J=7.6 Hz, 1H), 5.05 (s, 2H); EIMS m/z 283.1.

Example 48: Preparation of 2-(2-Chloro-4-vinylbenzyl)isoindoline-1,3-dione (CI22)

To a stirred solution of 3-chloro-4-((1,3-dioxoisoindolin-2-yl)methyl)benzaldehyde (2.8 g, 8.2 mmol) in 1,4-dioxane (30 mL) were added K₂CO₃ (1.68 g, 12.24 mmol) and methyl triphenyl phosphonium bromide (4.37 g, 12.24 mmol) at ambient temperature. Then the resultant reaction mixture was heated at 100° C. for 18 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to ambient temperature and filtered, and the obtained filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (SiO₂, 100-200 mesh; 20% EtOAc in n-Hexane) to afford the title compound as a white solid (1.94 g, 70%): mp 141-143° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.85 (m, 2H), 7.70 (m, 2H), 7.41 (m, 1H), 7.21 (m, 2H), 6.71 (dd, J=17.6, 10.8 Hz, 1H), 5.72 (d, J=17.6 Hz, 1H), 5.23 (d, J=10.8 Hz, 1H), 4.92 (s, 2H); ESIMS m/z 298.10 ([M−H]⁻).

The following compounds were made in accordance with the procedures disclosed in Example 48.

2-(2-(Trifluoromethyl)-4-vinylbenzyl)isoindoline-1,3-dione (CI23)

The title compound was isolated as a light brown solid (0.5 g, 60%): mp 134-135° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.92 (m, 2H), 7.80 (m, 2H), 7.71 (s, 1H), 7.46 (d, J=8.0 Hz, 1H), 7.16 (d, J=8.0 Hz, 1H), 6.65 (m, 1H), 5.80 (d, J=17.8 Hz, 1H), 5.19 (d, J=10.8 Hz, 1H), 5.09 (s, 2H); ESIMS m/z 332.10 ([M+H]⁺).

2-(2-Bromo-4-vinylbenzyl)isoindoline-1,3-dione (CI24)

The title compound was isolated as an off white solid (0.5 g, 62%): mp 126-128° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.92 (m, 2H), 7.79 (m, 2H), 7.62 (s, 1H), 7.21 (m, 1H), 7.16 (d, J=8.0 Hz, 1H), 6.62 (m, 1H), 5.72 (d, J=17.8 Hz, 1H), 5.15 (d, J=10.8 Hz, 1H), 4.95 (s, 2H); EIMS m/z 341.10.

2-(2-Fluoro-4-vinylbenzyl)isoindoline-1,3-dione (CI25)

The title compound was isolated as a white solid (0.5 g, 61%): mp 140-142° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.85 (m, 2H), 7.72 (m, 2H), 7.25 (m, 1H), 7.11 (m, 2H), 6.63 (m, 1H), 5.80 (d, J=17.6 Hz, 1H), 5.28 (d, J=10.8 Hz, 1H), 4.92 (s, 2H); EIMS m/z 282.08.

Example 49: Preparation of (E)-2-(2-Chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)isoindoline-1,3-dione (CI26)

To a stirred solution of 2-(2-chloro-4-vinylbenzyl)isoindoline-1,3-dione (2.0 g, 6.51 mmol) in 1,2-dichlorobenzene (25 mL) were added 1-(1-bromo-2,2,2-trifluoroethyl)-3,5-dichlorobenzene (3.48 g, 11.36 mmol), CuCl (112 mg, 1.13 mmol) and 2,2-bipyridyl (0.35 g). The resultant reaction mixture was degassed with argon for 30 min and then was stirred at 180° C. for 24 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to ambient temperature and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (SiO₂, 100-200 mesh; 25-30% EtOAc in n-hexane) to afford the title compound as solid (1.3 g, 50%): mp 141-143° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.92 (m, 2H), 7.79 (m, 2H), 7.42 (m, 2H), 7.24 (m, 2H), 7.20 (m, 2H), 6.54 (d, J=16.0 Hz, 1H), 6.34 (dd, J=16.0, 8.0 Hz, 1H), 5.00 (s, 2H), 4.10 (m, 1H); ESIMS m/z 524.07 ([M+H]⁺).

The following compounds were made in accordance with the procedures disclosed in Example 49.

(E)-2-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)isoindoline-1,3-dione (CI27)

The title compound was isolated as a pale white solid (0.2 g, 55%): mp 128-129° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.92 (m, 2H), 7.79 (m, 2H), 7.42 (m, 3H), 7.22 (m, 2H), 6.52 (d, J=16.0 Hz, 1H), 6.32 (dd, J=16.0, 8.0 Hz, 1H), 5.00 (s, 2H), 4.05 (m, 1H); ESIMS m/z 557.99 ([M+H]⁺).

(E)-2-(2-Chloro-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)isoindoline-1,3-dione (CI28)

The title compound was isolated as an off white solid (0.2 g, 54%): mp 177-180° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.90 (m, 2H), 7.77 (m, 2H), 7.42 (s, 1H), 7.32 (d, J=8.0 Hz, 2H), 7.21 (m, 2H), 6.52 (d, J=16.0 Hz, 1H), 6.32 (dd, J=16.0, 8.0 Hz, 1H), 5.00 (s, 2H), 4.05 (m, 1H); ESIMS m/z 540.08 ([M−H]⁻); IR (thin film) 1716 cm⁻¹.

(E)-2-(2-Chloro-4-(3-(3,4-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)isoindoline-1,3-dione (CI29)

The title compound was isolated as an off-white solid (0.2 g, 59%): ¹H NMR (400 MHz, CDCl₃) δ 7.89 (m, 2H), 7.76 (m, 2H), 7.47 (m, 3H), 7.21 (m, 3H), 6.50 (d, J=16.0 Hz, 1H), 6.32 (dd, J=16.0, 7.6 Hz, 1H), 4.97 (s, 2H), 4.11 (m, 1H); ESIMS m/z 522.27 ([M−H]⁻); IR (thin film) 3064, 1717, 1111, 715 cm⁻¹.

(E)-2-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(trifluoromethyl)-benzyl)isoindoline-1,3-dione (CI30)

The title compound was isolated as an off-white solid (0.2 g, 54%): mp 141-142° C.; ¹H NMR (400 MHz, CDCl₃) 7.94 (m, 2H), 7.80 (m, 2H), 7.69 (s, 1H), 7.44 (m, 1H), 7.38 (m, 1H), 7.24 (m, 2H), 7.19 (m, 1H), 6.60 (d, J=16.0 Hz, 1H), 6.39 (dd, J=16.0, 7.6 Hz, 1H), 5.10 (s, 2H), 4.11 (m, 1H); ESIMS m/z 556.00 ([M−H]⁻).

(E)-2-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)-benzyl)isoindoline-1,3-dione (CI31)

The title compound was isolated as an off-white solid (0.2 g, 56%): mp 130-132° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.94 (m, 2H), 7.80 (m, 2H), 7.69 (s, 1H), 7.44 (m, 3H), 7.19 (m, 1H), 6.61 (d, J=16.0 Hz, 1H), 6.38 (dd, J=16.0, 7.6 Hz, 1H), 5.10 (s, 2H), 4.12 (m, 1H); ESIMS m/z 589.57 ([M−2H]⁻).

(E)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)-isoindoline-1,3-dione (CI32)

The title compound was isolated as a pale yellow solid (0.2 g, 55%): mp 160-162° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.92 (m, 2H), 7.80 (m, 2H), 7.62 (s, 1H), 7.39 (s, 2H), 7.24 (m, 1H), 7.16 (m, 1H), 6.52 (d, J=16.0 Hz, 1H), 6.32 (dd, J=16.0, 8.0 Hz, 1H), 4.98 (s, 2H), 4.12 (m, 1H); ESIMS m/z 599.78 ([M−H]⁻).

(E)-2-(2-Fluoro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)-isoindoline-1,3-dione (CI33)

The title compound was isolated as an off-white solid (0.2 g, 55%): mp 72-74° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.88 (m, 2H), 7.74 (m, 2H), 7.38 (s, 2H), 7.34 (m, 1H), 7.18 (m, 2H), 6.54 (d, J=16.0 Hz, 1H), 6.32 (dd, J=16.0, 8.0 Hz, 1H), 4.91 (s, 2H), 4.08 (m, 1H); ESIMS m/z 539.89 ([M−H]⁻); IR (thin film) 1773 cm⁻¹.

Prophetically, compounds CI34-CI41 (Table 1) could be made in accordance with the procedures disclosed in Example 49.

Example 50: Preparation of (E)-(2-Chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine (CI42)

To a stirred solution of (E)-2-(2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)isoindoline-1,3-dione (0.4 g, 0.76 mmol) in EtOH was added hydrazine hydrate (0.38 g, 7.6 mmol), and the resultant reaction mixture was heated at 80° C. for 2 h. The reaction mixture was filtered, and the filtrate was concentrated. The residue was dissolved in CH₂Cl₂, washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure to afford the title compound as a gummy liquid (0.3 g), which was carried on to the next step without further purification.

The following compounds were made in accordance with the procedures disclosed in Example 50.

(E)-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)-methanamine (CI43)

The product obtained in this reaction was carried on to the next step without further purification.

(E)-(2-Chloro-4-(3-(3,4-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)-methanamine (CI44)

The product obtained in this reaction was carried on to the next step without further purification. ¹H NMR (400 MHz, CDCl₃) δ 7.48 (d, J=8.4 Hz, 2H), 7.39 (m, 2H), 7.23 (m, 2H), 6.52 (d, J=16.0 Hz, 1H), 6.38 (dd, J=16.0, 7.6 Hz, 1H), 4.12 (m, 1H), 3.90 (s, 2H); ESIMS m/z 391.90 ([M−H]⁻); IR (thin film) 3370, 3280, 1111, 817 cm⁻¹.

(E)-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)-phenyl)methanamine (CI45)

The title compound was isolated as a gummy material. The product obtained in this reaction was carried on to the next step without further purification.

(E)-(2-Bromo-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)-methanamine (CI46)

The title compound was isolated as a gummy material: The product obtained in this reaction was carried on to the next step without further purification.

(E)-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)-methanamine (CI47)

The title compound was isolated as a gummy material. The product obtained in this reaction was carried on to the next step without further purification.

(E)-(2-Fluoro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)-methanamine (CI48)

The title compound was isolated as a gummy material: ¹H NMR (400 MHz, CDCl₃) δ 7.40 (s, 2H), 7.33 (t, J=7.6 Hz, 1H), 7.13 (m, 2H), 6.56 (d, J=16.0 Hz, 1H), 6.33 (dd, J=16.0, 7.6 Hz, 1H), 4.08 (m, 1H), 3.90 (s, 2H); ESIMS m/z 413.84 ([M+H]⁺); IR (thin film) 3368, 3274, 1114, 808 cm⁻¹.

Prophetically, compounds CI49-CI57 (Table 1) could be made in accordance with the procedures disclosed in Example 50.

Example 51: Preparation of 3-Chloro-4-((pyridin-2-ylamino)methyl)benzaldehyde (CI58)

To a stirred solution of 4-(bromomethyl)-3-chlorobenzaldehyde (2 g, 9 mmol) in N,N-dimethylacetamide (DMA; 20 mL) was added K₂CO₃ (2.36 g, 17.16 mmol) and 2-aminopyridine (0.84 g, 8.58 mmol), and the reaction mixture was stirred at ambient temperature for 4 h. The reaction mixture was diluted with H₂O and extracted with EtOAc. The combined organic layer was washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure. The residue was purified by flash column chromatography (SiO₂, 100-200 mesh; 20% EtOAc in n-Hexane) to afford the title compound as off-white solid (1.05 g, 50%): mp 122-123° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.94 (s, 1H), 8.11 (s, 1H), 7.88 (s, 1H), 7.72 (d, J=4.8 Hz, 1H), 7.62 (d, J=5.7 Hz, 1H), 7.4 (m, 1H), 6.64 (d, J=3.9 Hz, 1H), 6.38 (d, J=6.3 Hz, 1H), 5.04 (br s, 1H), 4.71 (s, 2H); ESIMS m/z 246.97 ([M+H]⁺).

Example 52: Preparation of N-(2-Chloro-4-vinylbenzyl)pyridin-2-amine (CI59)

To a stirred solution of 3-chloro-4-((pyridin-2-ylamino)methyl)benzaldehyde (1 g, 4. mmol) in 1,4-dioxane (20 mL) were added K₂CO₃ (0.84 g, 6.09 mmol) and methyl triphenyl phosphonium bromide (2.17 g, 6.09 mmol) at ambient temperature. Then the resultant reaction mixture was heated at 100° C. for 18 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to ambient temperature and filtered, and the obtained filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (SiO₂, 100-200 mesh; 10% EtOAc in n-Hexane) to afford the title compound as a white solid (0.5 g, 50%): mp 119-121° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.12 (s, 1H), 7.42-7.40 (m, 3H), 7.26 (s, 1H), 6.66 (m, 2H), 6.36 (d, J=6.3 Hz, 1H), 5.75 (d, J=13.2 Hz, 1H), 4.92 (br s, 1H), 4.60 (s, 2H); ESIMS m/z 245.05 ([M+H]⁺).

Example 53: Preparation of Ethyl 2-amino-2-(5-bromo-3-chloropyridin-2-yl)acetate (CI60)

Ethyl 2-(diphenylmethyleneamino)acetate (10.2 g, 38.2 mmol) was added to sodium hydride (NaH; 3.18 g, 133.52 mmol) in DMF (50 mL) at 0° C., and the mixture was stirred for 30 min. To this was added 5-bromo-2,3-dichloropyridine (12.9 g, 57.23 mmol), and the reaction mixture was stirred for 3 h at ambient temperature. The reaction mixture was quenched with 2 N HCl solution and then stirred for 4 h at ambient temperature. The mixture was extracted with EtOAc. The combined EtOAc layer was washed with brine, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. Purification by flash column chromatography (20-30% EtOAc in hexane) afforded the title compound as a liquid (1.3 g, 20%): ¹H NMR (400 MHz, CDCl₃) δ 8.52 (s, 1H), 7.89 (s, 1H), 5.09 (s 1H), 4.23 (m, 2H), 2.27 (br s, 2H), 1.26 (m, 3H); ESIMS m/z 293.05 ([M+H]⁺); IR (thin film) 3381, 3306, 1742, 759, 523 cm⁻¹.

Example 54: Preparation of (5-Bromo-3-chloropyridin-2-yl)methanamine hydrochloride (CI61)

A stirred solution of ethyl 2-amino-2-(5-bromo-3-chloropyridin-2-yl)acetate (0.5 g, 1.7 mmol) in 3 N HCl (25 mL) was heated at reflux for 4 h. The reaction mixture was washed with diethyl ether and H₂O. The combined ether layer was concentrated under reduced pressure to afford the title compound as an off-white solid (400 mg, 65%): ¹H NMR (400 MHz, CDCl₃) δ 8.78 (s, 1H), 8.70 (br s, 2H), 8.45 (s, 1H), 4.56 (m, 2H); ESIMS m/z 221.15 ([M+H]⁺).

Example 55: Preparation of 2-((5-Bromo-3-chloropyridin-2-yl)methyl)isoindoline-1,3-dione (CI62)

To a stirred solution of (5-bromo-3-chloropyridin-2-yl)methanamine hydrochloride (0.3 g, 1.4 mmol) in toluene (40 mL) was added Et₃N (0.41 g, 4.08 mmol) and phthalic anhydride (0.24 g, 1.63 mmol), and the reaction mixture was heated at reflux for 2 h. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with H₂O and extracted with EtOAc. The combined EtOAc layer was washed with brine, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. The residue was purified by column chromatography (20-30% EtOAc in hexane) to afford the title compound as a white solid (0.25 g, 65%): ¹H NMR (400 MHz, CDCl₃) δ 8.78 (s, 1H), 8.45 (s, 1H), 7.88 (m, 2H), 7.74 (m, 2H), 4.56 (m, 2H); ESIMS m/z 349 ([M−H]⁻); IR (thin film) 3307, 1665, 1114, 813 cm⁻¹.

Example 56: Preparation of 2-((3-Chloro-5-vinylpyridin-2-yl)methyl)isoindoline-1,3-dione (CI63)

To a stirred solution of 2-((5-bromo-3-chloropyridin-2-yl)methyl)isoindoline-1,3-dione (0.23 g, 0.65 mmol) in toluene (10 mL) were added Pd(PPh₃)₄ (3.7 mg, 0.003 mmol), K₂CO₃ (0.269 g, 1.95 mmol) and vinyl boronic anhydride pyridine complex (0.78 g, 3.28 mmol), and the reaction mixture was heated at reflux for 16 h. The reaction mixture was filtered, and the filtrate was washed with H₂O and brine, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. Purification by flash column chromatography (20-30% EtOAc in hexane) afforded the title compound as an off-white solid (0.2 g, 65%): ¹H NMR (400 MHz, CDCl₃) δ 8.30 (s, 1H), 7.91 (m, 2H), 7.77 (m, 3H), 7.72 (m, 1H), 6.63 (m, 1H), 5.79 (d, J=16.0 Hz, 1H), 5.39 (d, J=16.0 Hz, 1H), 5.12 (s, 2H); ESIMS m/z 299.20 ([M+H]⁺).

Example 57: Preparation of (E)-2-((3-Chloro-5-(4,4,4-trifluoro-3-(3,4,5-trichloro-phenyl)but-1-en-1-yl)pyridin-2-yl)methyl)isoindoline-1,3-dione (CI64)

To a stirred solution of 2-((3-chloro-5-vinylpyridin-2-yl)methyl)isoindoline-1,3-dione (0.35 g, 1.17 mmol) in 1,2-dichlorobenzene (10 mL) were added 5-(1-bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (0.8 g, 2.3 mmol), CuCl (23 mg, 0.12 mmol), 2,2-bipyridyl (0.073 g, 0.234 mmol), and the reaction mixture was heated at 180° C. for 16 h. The reaction mixture was concentrated under reduced pressure and purified by column chromatography (20-30% EtOAc in hexane) to afford the title compound as a liquid (0.4 g, 50%): mp 79-82° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.27 (s, 1H), 7.91 (m, 2H), 7.77 (m, 3H), 7.36 (s, 2H), 6.51 (d, J=15.6 Hz, 1H), 6.32 (dd, J=15.6, 8.0 Hz, 1H), 5.30 (s, 2H), 4.13 (m, 1H); ESIMS m/z 559 ([M+H]⁺).

Example 58: Preparation of (E)-(3-Chloro-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)pyridin-2-yl)methanamine (CI65)

To a stirred solution of (E)-2-((3-chloro-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)pyridin-2-yl)methyl)isoindoline-1,3-dione (200 mg, 0.358 mmol) in EtOH (5 mL) was added hydrazine hydrate (89.6 mg, 1.79 mmol), and the reaction mixture was heated at reflux for 2 h. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in CH₂Cl₂. The organic layer was washed with H₂O and brine, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure to afford the title compound as a solid (100 mg). The product obtained in this reaction was carried on to the next step without further purification.

Example 59: Preparation of 4-(Bromomethyl)-1-naphthonitrile (CI66)

To a stirred solution of 4-methyl-1-naphthonitrile (5 g, 30 mmol) in CCl₄ (50 mL) under argon atmosphere was added NBS (6.06 g, 34.09 mmol), and the reaction mixture was degassed for 30 min. AIBN (0.3 g, 2.1 mmol) was added, and the resultant reaction mixture was heated at reflux for 4 h. The reaction mixture was cooled to ambient temperature, diluted with H₂O and extracted with CH₂Cl₂ (3×100 mL). The combined CH₂Cl₂ layer was washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure. The residue was purified by flash column chromatography (SiO₂, 100-200 mesh; 5% EtOAc in n-Hexane) to afford the title compound as a white solid (3.8 g, 52%): mp 131-133° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.33 (m, 1H), 8.24 (m, 1H), 7.88 (d, J=8.0 Hz, 1H), 7.78 (m, 2H), 7.62 (d, J=8.0 Hz, 1H), 4.95 (s, 2H); ESIMS m/z 245.92 ([M+H]⁺); IR (thin film) 2217 cm⁻¹.

Example 60: Preparation of 4-(Bromomethyl)-1-naphthaldehyde (CI67)

To a stirred solution of 4-(bromomethyl)-1-naphthonitrile (8 g, 33 mmol) in toluene (100 mL) at 0° C. was added dropwise DIBAL-H (1.0 M solution in toluene; 43 mL), and the reaction mixture was stirred at 0° C. for 1 h. 3 N HCl in H₂O (50 mL) was added to the mixture until it became a white slurry and then additional 1 N HCl (20 mL) was added. The organic layer was collected and the aqueous layer was extracted with EtOAc (3×100 mL). The combined organic layer was dried over Na₂SO₄ and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 100-200 mesh; 5% EtOAc in petroleum ether) afforded the title compound as a white solid (7 g, 88%): mp 115-116° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.41 (s, 1H), 9.35 (m, 1H), 8.22 (m, 1H), 7.90 (d, J=8.0 Hz, 1H), 7.75 (m, 3H), 4.95 (s, 2H); ESIMS m/z 248.88 ([M+H]⁺).

Example 61: Preparation of 4-((1,3-Dioxoisoindolin-2-yl)methyl)-1-naphthaldehyde (CI68)

To a stirred solution of 4-(bromomethyl)-1-naphthaldehyde (7 g, 28 mmol) in DMF (100 mL) was added potassium phthalimide (7.3 g, 39.5 mmol), and the mixture was heated at 85° C. for 2 h. The reaction mixture was cooled to ambient temperature and diluted with H₂O (100 mL). The obtained solid was separated by filtration and dried under vacuum to afford the title compound as a white solid (8.8 g, 98%): mp 190-192° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.39 (s, 1H), 9.25 (m, 1H), 8.41 (m, 1H), 8.10 (d, J=8.0 Hz, 1H), 7.95 (m, 4H), 7.80 (m, 4H), 7.61 (m, 4H), 5.39 (s, 2H); ESIMS m/z 316.09 ([M+H]⁺); IR (thin film) 1708 cm⁻¹.

Example 62: Preparation of 2-((4-Vinylnaphthalen-1-yl)methyl) isoindoline-1,3-dione (CI69)

To a stirred solution of 4-((1,3-dioxoisoindolin-2-yl)methyl)-1-naphthaldehyde (9 g, 28.5 mmol) in 1,4-dioxane (100 mL) were added K₂CO₃ (6 g, 42.8 mmol) and methyl triphenyl phosphonium bromide (15.3 g, 35.7 mmol) at ambient temperature. The reaction mixture was heated at 100° C. for 14 h and then was cooled to ambient temperature. The reaction mixture was filtered, and the obtained filtrate was concentrated under reduced pressure. Purification by flash chromatography (SiO₂, 100-200 mesh; 20% EtOAc in petroleum ether) afforded the title compound as a white solid (6 g, 67%): mp 146-147° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.35 (m, 2H), 7.95 (m, 4H), 7.65 (m, 4H), 7.39 (m, 1H), 5.81 (m, 1H), 5.45 (m, 1H), 5.21 (s, 2H); ESIMS m/z 314.13 ([M+H]⁺).

Example 63: Preparation of (E)-2-((4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methyl)isoindoline-1,3-dione (CI70)

To a stirred solution of 2-((4-vinylnaphthalen-1-yl)methyl)isoindoline-1,3-dione (1.5 g, 4.79 mmol) in 1,2-dichlorobenzene (15 mL) were added 1-(1-bromo-2,2,2-trifluoroethyl)-3,4,5-trichlorobenzene (3.2 g, 9.5 mmol), CuCl (24 mg, 0.24 mmol) and 2,2-bipyridyl (0.149 g, 0.95 mmol), and the resultant reaction mixture was degassed with argon for 30 min and then stirred at 180° C. for 14 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to ambient temperature and filtered, and the filtrate was concentrated under reduced pressure. Purification by flash chromatography (SiO₂, 100-200 mesh; 25-30% EtOAc in petroleum ether) afforded the title compound as an off-white solid (1.5 g, 56%): mp 158-160° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.40 (m, 1H), 7.89 (m, 2H), 7.74 (m, 2H), 7.64 (m, 2H), 7.58 (m, 2H), 7.46 (s, 2H), 7.36 (m, 2H), 6.31 (m, 1H), 5.30 (s, 2H), 4.21 (m, 1H); ESIMS m/z 572.08 ([M−H]⁻).

Example 64: Preparation of (E)-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methanamine (CI71)

To a stirred solution of (E)-2-((4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methyl)isoindoline-1,3-dione (0.4 g, 0.7 mmol) in EtOH was added hydrazine hydrate (0.18 g, 3.5 mmol), and the resultant reaction mixture was heated at 80° C. for 2 h. The reaction mixture was filtered, and the filtrate was concentrated. The residue was dissolved in CH₂Cl₂, and the solution was washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure. The title compound was isolated as a gummy liquid (150 mg, 50%). The product obtained in this reaction was carried on to the next step without further purification.

Example 65: Preparation of 2-((4-Bromophenyl)amino)isoindoline-1,3-dione (CI72)

To a stirred solution of (4-bromophenyl)hydrazine hydrochloride (0.5 g, 2.2 mmol) in glacial acetic acid (8 mL) was added phthalic anhydride (0.398 g, 2.690 mmol), and the reaction mixture was stirred at 130° C. for 1 h under a nitrogen atmosphere. The reaction mixture was quenched with satd aq. NaHCO₃ solution and filtered to give a solid. Purification by column chromatography (SiO₂, 0-10% EtOAc in petroleum ether) afforded the title compound as a solid (60 mg, 84%): mp 205-206° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.71 (s, 1H), 7.99 (m, 4H), 7.32 (d, J=8.8 Hz, 2H), 6.79 (d, J=8.8 Hz, 2H); ESIMS m/z 314.95 ([M−H]⁻).

Example 66: Preparation of 2-((4-Vinylphenyl)amino)isoindoline-1,3-dione (CI73)

To a solution of 2-(4-bromophenylamino)isoindoline-1,3-dione (2 g, 6 mmol) in 1,2-dimethoxyethane (20 mL) and H₂O (4 mL) were added vinyl boronic anhydride pyridine complex (4.57 g, 18.98 mmol) and K₂CO₃ (1.3 g, 9.5 mmol) followed by Pd(PPh₃)₄ (0.219 g, 0.189 mmol). The resultant reaction mixture was heated at 150° C. in a microwave for 30 min and then was concentrated under reduced pressure. Purification by column chromatography (SiO₂, 15% EtOAc in petroleum ether) afforded the title compound as a solid (200 mg, 13%): mp 174-176° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.65 (s, 1H), 7.94 (m, 4H), 7.29 (d, J=8.4 Hz, 2H), 6.72 (d, J=8.4 Hz, 2H), 6.61 (m, 1H), 5.61 (d, J=17.6 Hz, 1H), 5.05 (d, J=11.2 Hz, 1H); ESIMS m/z 263.18 ([M−H]⁻).

Example 67: Preparation of (E)-2-((4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)amino)isoindoline-1,3-dione (CI74)

To a stirred solution of 2-(4-vinylphenylamino)isoindoline-1,3-dione (0.3 g, 1.1 mmol) in 1,2-dichlorobenzene (5 mL) were added CuCl (0.022 g, 0.273 mmol), 2,2-bipyridyl (0.07 g, 0.46 mmol) and 5-(1-bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (0.77 g, 2.27 mmol). The reaction mixture was degassed with argon for 30 min and was heated at 180° C. for 2 h. The reaction mixture was then concentrated under reduced pressure, and the residue was purified by column chromatography (SiO₂, 0-30% EtOAc in petroleum ether) to afford the title compound as a solid (450 mg, 75%): mp 187-189° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.75 (s, 1H), 7.96 (m, 4H), 7.82 (s, 2H), 7.37 (d, J=8.8 Hz, 1H), 6.73 (d, J=8.4 Hz, 2H), 6.61 (m, 2H), 6.58 (m, 1H), 4.59 (m, 1H); ESIMS m/z 523.05 ([M−H]⁻).

Example 68: Preparation of (E)-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)hydrazine (CI75)

To a stirred solution of (E)-2-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)phenylamino)isoindoline-1,3-dione (0.16 g, 0.31 mmol) in EtOH (5 mL), was added hydrazine hydrate (0.076 g, 1.52 mmol), and the reaction mixture was heated at 85° C. for 1 h. The reaction mixture was cooled to ambient temperature and filtered, and the filtrate was concentrated under reduced pressure to afford the title compound as a solid (0.08 g, 66%) which was carried on to the next step without further purification.

Example 69: Preparation of 2-(4-Vinylphenoxy)isoindoline-1,3-dione (CI76)

To a stirred solution of 4-vinylphenylboronic acid (2 g, 13 mmol), 2-hydroxyisoindoline-1,3-dione (3.63 g, 24.53 mmol), and CuCl (1.214 g 12.26 mmol) in 1,2-dichloroethane (50 mL) was added pyridine (1.065 g, 13.48 mmol), and the resultant reaction mixture was stirred at ambient temperature for 48 h. The reaction mixture was diluted with H₂O and extracted with CHCl₃. The combined CHCl₃ layer was washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂; 20% EtOAc in petroleum ether) afforded the title compound as a white solid (2 g, 63%): mp 129-131° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.93 (d, J=2.0 Hz, 2H), 7.82 (d, J=3.2 Hz, 2H), 7.38 (d, J=2.0 Hz, 2H), 7.14 (d, J=2.0 Hz, 2H), 6.70 (m, 1H), 5.83 (d, J=16.0 Hz, 1H), 5.22 (d, J=10.8 Hz, 1H); ESIMS m/z 266.12 ([M+H]⁺).

Example 70: Preparation of (E)-2-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenoxy)isoindoline-1,3-dione (CI77)

To a stirred solution of 2-(4-vinylphenoxy)isoindoline-1,3-dione (0.3 g, 1.1 mmol) in 1,2-dichlorobenzene (10 mL) was added 1-(1-bromoethyl)-3,4,5-trichlorobenzene (769 mg, 2.26 mmol), CuCl (22 mg, 0.22 mmol) and 2,2-bipyridyl (35 mg, 0.44 mmol), and the resultant reaction mixture was degassed with argon for 30 min and heated to 180° C. for 24 h. The reaction mixture was cooled to ambient temperature and filtered, and the filtrate was concentrated under reduced pressure. The crude material was purified by column chromatography (SiO₂, 100-200 mesh; 20% EtOAc in petroleum ether) to afford the title compound as a solid (0.29 g, 50%): ¹H NMR (400 MHz, CDCl₃) δ 7.90 (m, 1H), 7.62 (m, 2H), 7.50 (m, 1H), 7.40 (s, 2H), 7.12 (s, 1H), 6.90 (m, 2H), 6.60 (m, 2H), 6.20 (m, 1H), 4.08 (m, 1H); ESIMS m/z 524.09 ([M−H]⁻).

Example 71: Preparation of (E)-O-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)hydroxylamine (CI78)

To a stirred solution of (E)-2-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)phenoxy)isoindoline-1,3-dione (0.2 g, 0.4 mmol) in EtOH was added hydrazine hydrate (0.1 g, 1.9 mmol), and the resultant reaction mixture was heated at 90° C. for 1 h. The reaction mixture was filtered, and the filtrate was concentrated. The residue was dissolved in CH₂Cl₂. washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure to afford the crude title compound as a gummy liquid (0.08 g, 53%): ¹H NMR (400 MHz, CDCl₃) δ 7.40 (s, 2H), 6.98 (s, 1H), 6.82 (s, 2H), 6.48 (m, 1H), 6.20 (m, 1H), 5.02 (s, 1H), 4.08 (m, 1H); ESIMS m/z 394.94 ([M−H]⁻).

Example 72: Preparation of (E)-N-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-enyl)benzyl)acetamide (CC1)

To a stirred solution of (E)-(2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine (0.3 g, 0.8 mmol) in DCM (10 mL) was added acetic anhydride (0.12 mL, 1.14 mmol), and TEA (0.217 mL, 1.52 mmol), and the resultant reaction mixture was stirred at ambient temperature for 6 h. The reaction mixture was diluted with H₂O and extracted with DCM. The combined DCM layer was washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 100-200 mesh; 30-50% ethyl acetate in hexane) afforded the title compound as an off-white solid (0.2 g, 60%) mp 107-109° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.37 (m, 3H), 7.28 (m, 4H), 6.60 (d, J=16.0 Hz, 1H), 6.36 (dd, J=16.0, 8.0 Hz, 1H), 5.75 (br s, 1H), 4.46 (d, J=6 Hz, 2H), 4.01 (m, 1H), 2.11 (s, 3H); ESIMS m/z 402.00 ([M+H]⁺).

Compounds CC2-CC6 in Table 1 were made in accordance with the procedures disclosed in Example 72. In addition, compound DC56 in Table 1 was made from compound DC55 in accordance with the procedures disclosed in Example 72.

Example 73: Preparation of (E)-N-(2-Chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)acetamide (CC7)

To a stirred solution of (E)-(2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine (0.3 g, 0.8 mmol) in DMF (5 mL) was added 2,2,2-trifluoropropanoic acid (97 mg, 0.76 mmol), HOBt.H₂O (174 mg, 1.14 mmol) and EDC.HCl (217 mg, 1.14 mmol) and DIEA (196 mg, 1.52 mmol), and the resultant reaction mixture was stirred at ambient temperature for 18 h. The reaction mixture was diluted with H₂O and extracted with EtOAc. The combined EtOAc layer was washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 100-200 mesh; ethyl acetate in hexane (30-50% afforded the title compound as an off-white solid (0.2 g, 60%): mp 127-128° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.42 (m, 4H), 7.24 (m, 2H), 6.53 (d, J=16.0 Hz, 1H), 6.36 (dd, J=16.0, 8.0 Hz, 1H), 5.86 (br s, 1H), 4.51 (d, J=6.0 Hz, 2H), 4.05 (m, 1H), 2.02 (s, 3H); ESIMS m/z 436.03 ([M+H]⁺).

Compounds CC8-CC28 in Table 1 were made in accordance with the procedures disclosed in Example 73.

Example 74: Preparation of (E)-N-(Pyridin-2-ylmethyl)-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)benzyl)cyclopropanecarboxamide (CC29)

Step 1: (E)-1-(Pyridin-2-yl)-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)benzyl)methanamine

(E)-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)phenyl)methanamine (0.46 g, 1 mmol) was dissolved in CH₃OH (3 mL). To this was added pyridine-2-carbaldehyde (0.107 g, 1 mmol). The reaction mixture was stirred for 1 h. After 1 h, NaBH₄ (0.076 g, 2 mmol) was added and left at ambient temperature for 3 h. The reaction mixture was concentrated to give an oily residue. Purification by flash column chromatography (SiO₂, 100-200 mesh; 30-50% EtOAc in hexane) afforded the title compound as a pale yellow liquid (0.22 g, 40%): ¹H NMR (400 MHz, CDCl₃) δ 8.58 (d, J=4.8 Hz, 1H), 7.74 (m, 1H), 7.62 (m, 2H), 7.52 (m, 1H), 7.4 (s, 2H), 7.3 (m, 1H), 7.2 (m, 2H), 6.60 (d, J=16.0 Hz, 1H), 6.38 (dd, J=16.0, 8.0 Hz, 1H), 4.10 (m, 1H), 4.02 (s, 2H), 3.96 (s, 2H); ESIMS m/z 552.95 ([M+H]⁺); IR (thin film) 3338, 1114, 808 cm⁻¹.

Step 2: (E)-N-(Pyridin-2-ylmethyl)-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2-(trifluoromethyl)benzyl)cyclopropanecarboxamide

(E)-1-(Pyridin-2-yl)-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzyl)methanamine (0.27 g, 0.05 mmol) was taken up in CH₂Cl₂ (3 mL). To this was added Et₃N (0.14 mL, 0.1 mmol). The reaction mixture was stirred for 10 min After 10 min, the reaction mixture was cooled to 0° C., and cyclopropylcarbonyl chloride (0.08 mL, 0.075 mmol) was added. The reaction mixture was stirred at ambient temperature for 1 h and then was washed with H₂O and satd aq NaHCO₃ solution. The organic layer was dried over anhydrous Na₂SO₄ and evaporated to obtain pale yellow gummy material (0.15 g, 50%): ¹H NMR (400 MHz, CDCl₃) δ 8.58 (d, J=4.6 Hz, 1H), 7.74 (m, 1H), 7.62 (m, 2H), 7.52 (m, 1H), 7.4 (s, 2H), 7.3 (m, 1H), 7.2 (m, 2H), 6.60 (d, J=16.0 Hz, 1H), 6.38 (dd, J=16.0, 8.0 Hz, 1H), 5.02 (s, 1H), 4.8 (s, 1H), 4.8 (d, J=10 Hz, 2H), 4.10 (m, 1H), 1.8 (m, 1H), 1.2 (m, 2H), 0.6 (m, 2H); ESIMS m/z 620.86 ([M−H]⁻); IR (thin film) 1645, 1115, 808 cm⁻¹.

Example 75: Preparation of (E)-N-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)-3-(methylsulfonyl)propanamide (CC30)

(E)-N-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)-3-(methylthio)propanamide (0.15 g, 0.28 mmol) was treated with oxone (0.175 g, 0.569 mmol) in 1:1 acetone:water (20 mL) for 4 h at ambient temperature. The acetone was evaporated to obtain a white solid (0.095 g, 60%): mp 101-104° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.41 (m, 4H), 7.24 (m, 1H), 6.53 (d, J=16.0 Hz, 1H), 6.35 (dd, J=16.0, 8.0 Hz, 1H), 6.12 (br s, 1H), 4.53 (m, 2H), 4.10 (m, 1H), 3.42 (m, 2H), 2.91 (s, 3H), 2.78 (m, 2H); ESIMS m/z 559.75 ([M−H]⁻).

Example 76: Preparation of (E)-1-(2-Chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)-3-ethylurea (CC31)

To a stirred solution of (E)-(2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine (0.2 g, 0.5 mmol) in CH₂Cl₂ (5 mL) at 0° C. were added Et₃N (0.141 mL, 1 mmol) and ethylisocyanate (0.053 g, 0.75 mmol), and the reaction mixture was stirred for 1 h at 0° C. The reaction mixture was diluted with CH₂Cl₂. The organic layer was washed with H₂O and brine, dried over Na₂SO₄, and concentrated under reduced pressure. Purification by column chromatography (SiO₂, 100-200 mesh; 30-50% EtOAc in hexane) afforded the title compound as a solid (0.141 g, 60%): mp 177-178° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.58 (m, 2H), 7.41 (m, 3H), 7.24 (m, 1H), 6.53 (d, J=16.0 Hz, 1H), 6.35 (dd, J=16.0, 8.0 Hz, 1H), 4.70 (br s, 1H), 4.43 (s, 2H), 4.08 (m, 1H), 3.21 (m, 2H), 1.25 (m, 3H); ESIMS m/z 463 ([M−H]⁻).

Compounds CC32-CC35 in Table 1 were made in accordance with the procedures disclosed in Example 76.

Example 77: Preparation of (E)-3-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)-1,1-dimethylurea (CC36)

To a stirred solution of (E)-(2-chloro-4-(3-(3,4,5-trichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine (0.2 g, 0.5 mmol) in CH₂Cl₂ (5 mL) at 0° C. were added Et₃N (0.141 mL, 1 mmol) and N,N-dimethylcarbamoyl chloride (0.08 g, 0.075 mmol), and the reaction mixture was stirred for 1 h at 0° C. The reaction mixture was diluted with CH₂Cl₂. The organic layer was washed with H₂O and brine, dried over Na₂SO₄, and concentrated under reduced pressure. Purification by column chromatography (SiO₂, 100-200 mesh; 30-50% EtOAc in hexane) afforded the title compound as a solid (0.15 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.39 (m, 4H), 7.28 (m, 1H), 6.54 (d, J=16.0 Hz, 1H), 6.34 (dd, J=16.0, 8.0 Hz, 1H), 4.97 (br s, 1H), 4.38 (d, J=6.0 Hz, 2H), 4.10 (m, 1H), 2.9 (s, 3H), 2.7 (s, 3H); ESIMS m/z 497 ([M−H]⁻); IR (thin film) 3350, 1705, 1114, 808 cm⁻¹.

Example 78: Preparation of (E)-1-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)-3-ethylthiourea (CC37)

To a stirred solution of (E)-(2-chloro-4-(3-(3,4,5-trichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine (0.2 g, 0.5 mmol) in CH₂Cl₂ (5 mL) at 0° C. were added Et₃N (0.141 mL, 1 mmol) and ethyl isothicyanate (0.053 g, 0.75 mmol), and the reaction mixture was stirred for 1 h at 0° C. The reaction mixture was diluted with CH₂Cl₂. The organic layer was washed with H₂O and brine, dried over Na₂SO₄, and concentrated under reduced pressure. Purification by column chromatography (SiO₂, 100-200 mesh; 30-50% EtOAc in hexane) afforded the title compound as a solid (0.14 g, 60%): mp 88-91° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.49 (d, J=8 Hz, 1H), 7.41 (d, J=7.2 Hz, 2H), 7.26 (m, 2H), 6.50 (d, J=16 Hz, 1H), 6.35 (dd, J=16.0, 8.0 Hz, 1H), 6.0 (br s, 1H), 5.73 (br s, 1H), 4.80 (br s, 2H), 4.09 (m, 1H), 1.23 (m, 3H); ESIMS m/z 515.01 ([M+H]⁺).

Compound CC38 in Table 1 was made in accordance with the procedures disclosed in Example 78.

Example 79: Preparation of (E)-tert-Butyl (2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)benzyl)-3-ethylurea (CC39)

To a stirred solution of (E)-(2-chloro-4-(3-(3,4,5-trichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine (0.2 g, 0.5 mmol in CH₂Cl₂ (5 mL) at 0° C. were added Et₃N (0.141 mL, 1 mmol) and di-tert-butyl dicarbonate (0.163 mL, 0.75 mmol), and the reaction mixture was stirred for 4 h at ambient temperature. The reaction mixture was diluted with CH₂Cl₂. The organic layer was washed with H₂O and brine, dried over Na₂SO₄, and concentrated under reduced pressure. Purification by column chromatography (SiO₂, 100-200 mesh; 10-20% EtOAc in hexane) afforded the title compound as a white solid (0.147 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.39 (m, 4H), 7.28 (m, 1H), 6.54 (d, J=16.0 Hz, 1H), 6.34 (dd, J=16.0, 8.0 Hz, 1H), 4.97 (br s, 1H), 4.38 (d, J=6.0 Hz, 2H), 4.10 (m, 1H), 1.53 (s, 9H); ESIMS m/z 526.09 ([M−H]⁻); IR (thin film) 3350, 1705, 1114, 808 cm⁻¹.

Compound CC40 in Table 1 was made in accordance with the procedures disclosed in Example 79.

Example 80: Preparation of (E)-Methyl 2-((2-chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)amino)-2-oxoacetate (CC41)

To a stirred solution of (E)-(2-chloro-4-(3-(3,4,5-trichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)methanamine (0.2 g, 0.5 mmol) in CH₂Cl₂ (5 mL) at 0° C. were added Et₃N (0.141 mL, 1 mmol) and methyl 2-chloro-2-oxoacetate (0.09 g, 0.75 mmol), and the reaction mixture was stirred for 1 h at 0° C. The reaction mixture was diluted with CH₂Cl₂. The organic layer was washed with H₂O and brine, dried over Na₂SO₄, and concentrated under reduced pressure. Purification by column chromatography (SiO₂, 100-200 mesh; 20% EtOAc in hexane) afforded the title compound as a solid (0.12 g, 50%): ¹H NMR (400 MHz, CDCl₃) δ 7.48 (m, 1H). 7.43 (m, 3H), 7.38 (m, 1H), 7.23 (s, 1H), 6.55 (d, J=16.0 Hz, 1H), 6.36 (dd, J=16.0, 8.0 Hz, 1H), 4.60 (d, J=4.4 Hz, 2H), 4.18 (m, 1H), 3.85 (s, 3H); ESIMS m/z 512.22 ([M−H]⁻); IR (thin film) 1740, 1701, 1114, 808 cm⁻¹.

Example 81: Preparation of (E)-N¹-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)-N²-(2,2,2-trifluoroethyl)oxalamide (CC42)

To a stirred solution of 2,2,2-trifluoroethylamine hydrochloride (0.1 g, 0.77 mmol) in CH₂Cl₂ (10 mL) was added dropwise trimethylaluminum (2 M solution in toluene; 0.39 mL, 0.77 mmol), and the reaction mixture was stirred at 25° C. for 30 min. A solution of (E)-methyl 2-((2-chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)-2-oxoacetate (0.2 g, 0.38 mmol) in CH₂Cl₂ (5 mL) was added dropwise to the reaction mixture at 25° C. The reaction mixture was stirred at reflux for 18 h, cooled to 25° C., quenched with 0.5 N HCl solution (50 mL) and extracted with EtOAc (2×50 mL). The combined organic extracts were washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure. The crude compound was purified by flash chromatography (SiO₂, 100-200 mesh; 20%-40% EtOAc in n-hexane) to afford the title compound (0.13 g, 60%): mp 161-163° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 9.45 (br s, 2H), 7.90 (s, 2H), 7.75 (s, 1H), 7.46 (s, 1H), 7.28 (s, 1H), 6.93 (m, 1H), 6.75 (m, 1H), 4.80 (m, 1H), 4.40 (s, 2H), 3.90 (s, 2H); ESIMS m/z 578.96 ([M−H]⁻).

Example 82: Preparation of (E)-N-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)pyridin-2-amine (CC43)

To a stirred solution of N-(2-chloro-4-vinylbenzyl)pyridin-2-amine (0.3 g, 1.22 mmol) in 1,2-dichlorobenzene (5 mL) were added 5-(1-bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (0.83 g, 2.44 mmol), CuCl (24 mg, 0.24 mmol) and 2,2-bipyridyl (76 mg, 0.48 mmol). The resultant reaction mixture was degassed with argon for 30 min and then stirred at 180° C. for 24 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to ambient temperature and filtered, and the filtrate was concentrated under reduced pressure. Purification by flash chromatography (SiO₂, 100-200 mesh; 15% EtOAc in n-hexane) afforded the title compound as an off-white solid (0.2 g, 35%): mp 140-142° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.11 (d, J=4.0 Hz, 1H), 7.40 (m, 5H), 7.22 (m, 1H), 6.61 (m, 2H), 6.35 (m, 2H), 4.94 (br s, 1H), 4.61 (d, J=6.4 Hz, 2H), 4.11 (m, 1H); ESIMS m/z 505.39 ([M+H]⁺).

Example 83: Preparation of (E)-N-((3-Chloro-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)-but-1-en-1-yl)pyridin-2-yl)methyl)-3,3,3-trifluoropropanamide (CC44)

To a stirred solution of (E)-(3-chloro-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)pyridin-2-yl)methanamine (0.1 g, 0.2 mmol) in CH₂Cl₂ (5 mL) were added 3,3,3-trifluoropropanoic acid (45 mg, 0.350 mmol), EDC.HCl (67 mg, 0.350 mmol), HOBt.H₂O (71 mg, 0.467 mmol) and DIEA (60.2 mg, 0.467 mmol), and the reaction mixture was stirred at ambient temperature for 18 h. The reaction mixture was diluted with CH₂Cl₂ and washed with H₂O. The combined CH₂Cl₂ layer was washed with brine, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 100-200 mesh; 15% EtOAc in petroleum ether) afforded the title compound as a pale yellow liquid (30 mg, 35%): ¹H NMR (400 MHz, CDCl₃) δ 8.41 (s, 1H), 7.77 (s, 1H), 7.47 (br s, 1H), 7.40 (s, 2H), 6.58 (d, J=16.0 Hz, 1H), 6.45 (dd, J=16.0, 8.0 Hz, 1H), 4.68 (d, J=4.0 Hz, 2H), 4.14 (m, 1H), 3.24 (q, J=10.8 Hz, 2H); ESIMS m/z 536.88 ([M−H]⁻); IR (thin film) 3320, 1674, 1114, 808.

Compound CC45 in Table 1 was made in accordance with the procedures disclosed in Example 83.

Example 84: Preparation of (E)-3,3,3-Trifluoro-N-((4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methyl)propanamide (CC46)

To a stirred solution of (E)-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methanamine (0.1 g, 0.22 mmol) in CH₂Cl₂ (8 mL) were added 3,3,3-trifluoropropanoic acid (0.032 g, 0.24 mmol), HOBt.H₂O (52 mg, 0.33 mmol), EDC.HCl (0.065 g, 0.33 mmol) and DIEA (0.044 g, 0.45 mmol), and the resultant reaction mixture was stirred at ambient temperature for 18 h. The reaction mixture was diluted with H₂O and extracted with EtOAc (3×30 mL). The combined EtOAc layer was washed with brine, dried over Na₂SO₄, and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 100-200 mesh; 15% EtOAc in n-hexane) afforded the title compound as a gummy material (60 mg, 50%): mp 151-153° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.06 (m, 1H), 7.61 (m, 4H), 7.48 (s, 2H), 7.44 (d, J=8.0 Hz, 1H), 7.38 (m, 1H), 6.42 (m, 1H), 5.92 (br s, 1H), 4.92 (m, 2H), 4.24 (m, 1H), 3.12 (m, 2H); ESIMS m/z 554.04 ([M−H]⁻).

Compounds CC47-CC48 in Table 1 were made in accordance with the procedures disclosed in Example 84.

Example 85: Preparation of (E)-1-Ethyl-3-((4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methyl)urea (CC49)

To a stirred solution of (E)-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)naphthalen-1-yl)methanamine (0.1 g, 0.22 mmol) in CH₂Cl₂ at 0° C. were added Et₃N (0.064 mL, 0.44 mmol) and ethylisocyanate (0.023 mL, 0.33 mmol), and the reaction mixture was stirred for 1 h at 0° C. The reaction mixture was diluted with CH₂Cl₂. The organic layer was washed with H₂O and brine, dried over Na₂SO₄, and concentrated under reduced pressure. Purification by column chromatography (SiO₂, 100-200 mesh; 30% EtOAc in hexane) afforded the title compound as a solid (0.07 g, 60%): mp 84-87° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.06 (m, 1H), 7.98 (m, 1H), 7.61 (m, 3H), 7.48 (s, 2H), 7.44 (d, J=8.0 Hz, 1H), 7.38 (m, 2H), 6.42 (m, 1H), 4.92 (s, 2H), 4.6 (br s, 1H), 4.24 (m, 1H), 3.21 (m, 2H), 1.2 (t, J=4.6 Hz, 3H); ESIMS m/z 515.33 ([M+H]⁺).

Example 86: Preparation of (E)-N′-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)cyclopropanecarbohydrazide (CC50)

To a stirred solution of (E)-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)hydrazine (0.1 g, 0.3 mmol) in CH₂Cl₂ (10 mL) was added DIEA (65 mg, 0.51 mmol), HOBt.H₂O (59 mg, 0.38 mmol), EDC.HCl (73 mg, 0.38 mmol) and cyclopropanecarbonyl chloride (0.024 g, 0.28 mmol), and the reaction mixture was stirred at ambient temperature for 1 h. The reaction mixture was diluted with satd aq NaHCO₃ solution and extracted with CH₂Cl₂. The combined CH₂Cl₂ layer was washed with brine, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂; 5-25% EtOAc in petroleum ether) afforded the title compound as a solid (65 mg, 55%): mp 138-140° C.; ¹H NMR (400 MHz, CDCl₃) δ 9.81 (s, 1H), 7.90 (s, 1H), 7.84 (s, 2H), 7.34 (d, J=8.4 Hz, 2H), 6.65 (d, J=15.6 Hz, 1H), 6.61 (m, 1H), 6.57 (s, 1H), 6.48 (dd, J=15.6, 8.8 Hz, 1H), 4.74 (m, 1H), 1.64 (m, 1H), 0.75 (m, 4H); ESIMS m/z 461.32 ([M−H]⁻).

Compound CC51 in Table 1 was made in accordance with the procedures disclosed in Example 86.

Example 87: Preparation of (E)-N-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenoxy)cyclopropanecarboxamide (CC52)

To a stirred solution of (E)-O-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)hydroxylamine (0.15 g, 0.38 mmol) in CH₂Cl₂ (5 mL) was added EDC.HCl (0.109 g, 0.569 mmol), HOBt.H₂O (0.087 g, 0.569 mmol), DIEA (0.097 g, 0.758 mmol) and cyclopropanecarboxylic acid (0.049 g, 0.569 mmol). The resultant reaction mixture was stirred at ambient temperature for 18 h. The reaction mixture was diluted with H₂O and extracted with CHCl₃ (35 mL) The combined CHCl₃ layer was washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂; 20% EtOAc in hexane) afforded the title compound as a brown liquid (0.06 g, 34%): ¹H NMR (400 MHz, CDCl₃) δ 7.40 (s, 2H), 7.18 (s, 1H), 7.08 (s, 1H), 6.85 (m, 1H), 6.45 (m, 1H), 6.65 (m, 1H), 6.20 (m, 1H), 5.55 (s, 1H), 4.08 (m, 1H), 1.90 (m, 1H), 1.30-1.10 (m, 4H); ESIMS m/z 464.87 ([M−H]⁻).

Compound CC53 in Table 1 was made in accordance with the procedures disclosed in Example 87.

Example 88: Preparation of (Z)-3,3,3-Trifluoro-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)propanamide (CC54)

A silicon borate vial was charged with (E)-3,3,3-trifluoro-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzyl)propanamide (133 mg, 0.269 mmol) and dimethyl sulfoxide (DMSO; 10 mL). The mixture was placed within 0.6 to 1 meter (m) of a bank of eight 115 watt Sylvania FR48T12/350BL/VHO/180 Fluorescent Tube Black Lights and four 115 watt Sylvania (daylight) F48T12/D/VHO Straight T12 Fluorescent Tube Lights for 72 h. The mixture was concentrated in vacuo and purified by reverse phase chromatography to give the title compound as a colorless oil (11 mg, 8%): ¹H NMR (300 MHz, CDCl₃) δ 7.28 (s, 2H), 7.25 (m, 2H), 7.10 (d, J=8.0 Hz, 2H), 6.89 (d, J=11.4 Hz, 1H), 6.07 (br s, 1H), 6.01 (m, 1H), 4.51 (d, J=5.8 Hz, 2H), 4.34 (m, 1H), 3.12 (q, J=7.5 Hz, 2H); ¹³C NMR (101 MHz, CDCl₃) δ 162.44, 137.20, 135.38, 135.23, 134.82, 134.68, 131.71, 129.00, 128.80, 128.69, 128.10, 127.96, 122.63, 76.70, 47.33 (q, J=28 Hz), 43.59, 42.12 (q, J=30 Hz); ESIMS m/z 504 ([M+H]⁺).

Compounds DC46, AC93. AC94 in Table 1 were made in accordance with the procedures disclosed in Example 88.

Example 89: Preparation of 1-(1-Bromo-2,2,2-trifluoroethyl)-3-chlorobenzene (DI2)

The title compound was synthesized in two steps via 1-(3-chlorophenyl)-2,2,2-trifluoroethanol (DI1, prepared as in Step 1, Method B in Example 1); isolated as a colorless viscous oil (1.5 g, 75%): ¹H NMR (400 MHz, CDCl₃) δ 7.50 (s, 1H), 7.42-7.35 (m, 3H), 5.02 (m, 1H), 2.65 (br s, 1H)) and Step 2 in Example 1 and isolated (0.14 g, 22%): ¹H NMR (400 MHz, CDCl₃) δ 7.50 (br s, 1H), 7.42-7.35 (m, 3H), 5.07 (m, 1H).

The following compounds were made in accordance with the procedures disclosed in Example 89.

(1-Bromo-2,2,2-trifluoroethyl)benzene (DI4)

2,2,2-Trifluoro-1-phenylethanol (DI3) was isolated (10 g, 80%): ¹H NMR (300 MHz, CDCl₃) δ 7.48 (m, 2H), 7.40 (m, 3H), 5.02 (m, 1H), 2.65 (d, J=7.1 Hz, 1H). The title compound (DI4) was isolated as a liquid (8.0 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.50 (m, 2H), 7.40 (m, 3H), 5.00 (q, J=7.5 Hz, 1H).

1-(1-Bromo-2,2,2-trifluoroethyl)-3,5-dimethylbenzene (DI20)

1-(3,5-Dimethylphenyl)-2,2,2-trifluoroethanol (DI19) was isolated an off white solid: ¹H NMR (400 MHz, CDCl₃) δ 7.05 (s, 2H), 7.02 (s, 1H), 4.95 (m, 1H), 2.32 (s, 6H); ESIMS m/z 204 ([M]⁻). The title compound (DI20) was isolated (3.0 g, 51%).

1-(1-Bromo-2,2,2-trifluoroethyl)-2,4-dichlorobenzene (DI22)

1-(2,4-Dichlorophenyl)-2,2,2-trifluoroethanol (DI21) was isolated as an off white powder (5.3 g, 61%): mp 49-51° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.62-7.66 (d, 1H), 7.42-7.44 (d, 1H), 7.32-7.36 (d, 1H), 5.6 (m, 1H), 2.7 (s, 1H); ESIMS m/z 244 ([M]⁺). The title compound (DI22) was isolated (3.2 g, 50%): ¹H NMR (400 MHz, CDCl₃) δ 7.62-7.72 (m, 1H), 7.4-7.42 (m, 1H), 7.3-7.38 (m, 1H), 5.7-5.8 (m, 1H).

1-(1-Bromo-2,2,2-trifluoroethyl)-2,3-dichlorobenzene (DI24)

1-(2,3-Dichlorophenyl)-2,2,2-trifluoroethanol (DI23) was isolated as a pale yellow oil (5.2 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.62-7.64 (d, 1H), 7.52-7.54 (m, 1H), 7.29-7.33 (t, 1H), 5.6-5.76 (m, 1H), 2.7 (s, 1H); ESIMS m/z 243.9 ([M]⁺). The title compound (DI24) was isolated as an oil (8.7 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.62-7.71 (m, 1H), 7.44-7.52 (m, 1H), 7.27-7.3 (s, 1H), 5.81-5.91 (m, 1H).

2-(1-Bromo-2,2,2-trifluoroethyl)-1,4-dichlorobenzene (DI26)

1-(2,5-Dichlorophenyl)-2,2,2-trifluoroethanol (DI25) was isolated as a yellow oil (4.1 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.68-7.7 (s, 1H), 7.3-7.37 (m, 2H), 5.51-5.6 (m, 1H), 2.7 (s, 1H); ESIMS m/z 244 ([M]⁺)). The title compound (DI26) was isolated (3.0 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.7-7.78 (m, 1H), 7.3-7.4 (m, 2H), 5.7-5.8 (m, 1H).

1-(1-Bromo-2,2,2-trifluoroethyl)-3,5-bis(trifluoromethyl)benzene (DI28)

1-(3,5-Bis(trifluoromethyl)phenyl)-2,2,2-trifluoroethanol (DI27) was isolated (3.8 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.98 (m, 3H), 5.25 (m, 1H), 3.2 (br, 1H); ESIMS m/z 312.2 ([M]⁺). The title compound (DI28) was prepared and carried on crude.

1-(1-Bromo-2,2,2-trifluoroethyl)-2,3,5-trichlorobenzene (DI30)

2,2,2-Trifluoro-1-(2,3,5-trichlorophenyl)ethanol (DI29) was isolated as a white solid (4.0 g, 60%): mp 113-115° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.62 (d, 1H), 7.50 (d, 1H), 5.60-5.70 (m, 1H), 2.75 (s, 1H); ESIMS m/z 278.0 ([M⁺]). The title compound (DI30) was isolated (2.9 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 7.70 (d, 1H), 7.50 (d, 1H), 5.72-5.82 (m, 1H).

1-(1-Bromo-2,2,2-trifluoroethyl)-3-chloro-5-(trifluoromethyl)benzene (DI32)

1-(3-Chloro-5-(trifluoromethyl)phenyl)-2,2,2-trifluoroethanol (DI31) was isolated as a pale yellow oil (2.0 g, 50%): ¹H NMR (400 MHz, CDCl₃) δ 7.51 (m, 3H), 5.08 (m, 1H), 2.81 (s, 1H); ESIMS m/z 278.1 ([M]⁺). The title compound (DI32) was isolated oil (2.0 g, 40%): ESIMS m/z 342 ([M]⁺).

5-(1-Bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-methoxybenzene (DI34)

1-(3,5-Dichloro-4-methoxyphenyl)-2,2,2-trifluoroethanol (DI33) was isolated as an off white solid (0.8 g, 60%); mp 92-95° C.: ¹H NMR (400 MHz, CDCl₃) δ 7.41 (s, 2H), 5.00 (m, 1H), 3.89 (s, 3H), 2.64 (m, 1H); ESIMS m/z 274 ([M]⁺). The title compound (DI34) was isolated as a colorless liquid (0.6 g, 57%).

Example 90: Preparation of 1-(1-Bromo-2,2,2-trifluoroethyl)-3,5-difluorobenzene (DI36)

The title compound was synthesized in two steps via 1-(3,5-difluorophenyl)-2,2,2-trifluoroethanol (DI35, prepared as in Step 1, Method A in Example 1; isolated as a colorless oil (0.2 g, 75%): ¹H NMR (400 MHz, CDCl₃) δ 7.05 (m, 2H), 6.88 (m, 1H), 5.06 (m, 1H), 2.66 (s, 1H); ESIMS m/z 212 ([M]⁺) and Step 2 in Example 1 and isolated (3.2 g, 50%); ¹H NMR (400 MHz, CDCl₃) δ 7.05 (m, 2H), 6.86 (m, 1H), 5.03 (q, J=7.4 Hz, 1H).

The following compounds were made in accordance with the procedures disclosed in Example 90.

1-(1-Bromo-2,2,2-trifluoroethyl)-4-chlorobenzene (DI38)

1-(4-Chlorophenyl)-2,2,2-trifluoroethanol (DI37) was isolated as a colorless oil (5.0 g, 99%): ¹H NMR (400 MHz, CDCl₃) δ 7.44-7.38 (m, 4H), 5.05 (m, 1H), 2.55 (s, 1H); ESIMS m/z 210 ([M]⁺). The title compound (DI38) was isolated (3.0 g, 46%): ¹H NMR (400 MHz, CDCl₃) δ 7.45 (d, J=8.2 Hz, 2H), 7.37 (d, J=8.2 Hz, 2H), 5.10 (q, J=7.2 Hz, 1H).

1-(1-Bromo-2,2,2-trifluoroethyl)-4-methoxybenzene (DI40)

2,2,2-Trifluoro-1-(4-methoxyphenyl)ethanol (DI39) was isolated as a pale yellow liquid: ¹H NMR (400 MHz, CDCl₃) δ 7.41 (d, J=8.8 Hz, 2H), 6.95 (m, J=8.8 Hz, 2H), 5.00 (m, 1H), 3.82 (s, 3H), 2.44 (s, 1H); ESIMS m/z 206.1 ([M]⁺). The title compound (DI40) was isolated (3.8 g, 62%).

1-(1-Bromo-2,2,2-trifluoroethyl)-4-fluorobenzene (DI42)

2,2,2-Trifluoro-1-(4-fluorophenyl)ethanol (DI41) was isolated as a colorless oil (5 g, 99%): ¹H NMR (400 MHz, CDCl₃) δ 7.48-7.45 (m, 2H), 7.13-7.07 (m, 2H), 5.06 (m, 1H), 2.53 (s, 1H); ESIMS m/z 194 ([M]⁺). The title compound (DI42) was prepared and carried on as crude intermediate.

1-(1-Bromo-2,2,2-trifluoroethyl)-4-methylbenzene (DI44)

2,2,2-Trifluoro-1-(p-tolyl)ethanol (DI43) was isolated as colorless oil (5.0 g, 99%): ¹H NMR (400 MHz, CDCl₃) δ 7.37 (d, J=8.0 Hz, 2H), 7.23 (d, J=8.0 Hz, 2H), 5.02 (m, 1H), 2.46 (m, 1H), 2.37 (s, 3H); ESIMS m/z 190 ([M]⁺). The title compound (DI44) was isolated (3.0 g, 45%).

1-(1-Bromo-2,2,2-trifluoroethyl)-3-fluorobenzene (DI46)

2,2,2-Trifluoro-1-(3-fluorophenyl)ethanol (DI45) was isolated as a colorless viscous oil (2.8 g, 93%): ¹H NMR (400 MHz, CDCl₃) δ 7.41 (m, 1H), 7.25 (m, 2H), 7.14 (m, 1H), 5.06 (m, 1H), 2.60 (s, 1H); ESIMS m/z 194 ([M]⁺). The title compound (DI46) was isolated (2.0 g, 61%).

1-(1-Bromo-2,2,2-trifluoroethyl)-2-fluorobenzene (DI48)

2,2,2-Trifluoro-1-(2-fluorophenyl)ethanol (DI47) was isolated as a colorless oil (2.5 g, 99%): ¹H NMR (400 MHz, CDCl₃) δ 7.40 (m, 1H), 7.43 (m, 1H), 7.24 (m, 1H), 7.13 (m, 1H), 5.42 (m, 1H), 2.65 (s, 1H); ESIMS m/z 194 ([M]⁺). The title compound (DI48) was isolated (2.0 g, 61%): ¹H NMR (400 MHz, CDCl₃) δ 7.61 (m, 1H), 7.40 (m, 1H), 7.23 (m, 1H), 7.10 (m, 1H), 5.40 (m, 1H); GCMS m/z 255 ([M−H]⁻).

Example 91: Preparation of 4-(1H-1,2,4-triazol-1-yl)benzaldehyde (DI5)

To a stirring solution of 4-fluorobenzaldehyde (10.0 g, 80.6 mmol) in DMF (150 mL) were added K₂CO₃ (13.3 g, 96.7 mmol) and 1,2,4-triazole (6.67 g, 96.7 mmol) and the resultant reaction mixture was stirred at 120° C. for 6 h. After completion of reaction (by TLC), the reaction mixture was diluted with H₂O and extracted with EtOAc (3×100 mL). The combined EtOAc layer was washed with H₂O and brine, dried over Na₂SO₄, and concentrated under reduced pressure to afford the title compound as a solid (9.0 g, 65%): mp 145-149° C.: ¹H NMR (400 MHz, CDCl₃) δ 10.08 (s, 1H), 8.70 (s, 1H), 8.16 (s, 1H), 8.06 (d, J=8.0 Hz, 2H), 7.92 (d, J=8.0 Hz, 2H); ESIMS m/z 173.9 ([M+H]⁺).

The following compound was made in accordance with the procedures disclosed in Example 91.

5-Formyl-2-(1H-1,2,4-triazol-1-yl)benzonitrile (DI49)

The title compound was isolated (2.8 g, 60%); ¹H NMR (400 MHz, CDCl₃) δ 10.10 (s, 1H), 8.98 (s, 1H), 8.35 (s, 1H), 8.30 (d, 1H), 8.22 (s, 1H), 8.07 (d, 1H); IR (thin film) 3433, 3120, 1702, 1599, 1510 cm⁻¹.

2-Chloro-4-(1H-1,2,4-triazol-1-yl)benzaldehyde (DI50)

The title compound was isolated as an off white solid (3.0 g, 40%): mp 149-151° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.05 (s, 1H), 8.74 (s, 1H), 8.17 (s, 1H), 8.10 (s, 1H), 7.90 (m, 2H); ESIMS m/z 208.10 ([M+H]⁺).

5-Methyl-4-(1H-1,2,4-triazol-1-yl)benzaldehyde (DI51)

The title compound was isolated as a white solid (0.5 g, 74%): mp 109-111° C.; ¹H NMR (400 MHz, D₆-DMSO) δ 10.06 (s, 1H), 9.00 (s, 1H), 8.30 (s, 1H), 7.99 (s, 1H), 7.92 (d, J=9.2 Hz, 1H), 7.69 (d, J=9.2 Hz, 1H), 2.30 (s, 3H); ESIMS m/z 188.13 ([M+H]⁺).

Example 92: Preparation of 5-Formyl-2-(3-nitro-1H-1,2,4-triazol-1-yl)benzonitrile (DI52)

To a stirring solution of 2-fluoro-5-formylbenzonitrile (0.5 g, 3.3 mmol) in DMF (25 mL) were added K₂CO₃ (0.68 g, 4.95 mmol) and 3-nitro-1,2,4 triazole (0.45 g, 4.2 mmol) and the resultant reaction mixture was stirred at RT for 14 h. After completion of reaction (TLC), the reaction mixture was diluted with water and extracted with EtOAc. The combined EtOAc layer was washed with water and brine then dried over Na₂SO₄ and concentrated under reduced pressure to afforded the title compound as a pale yellow solid (0.36 g, 45%): mp 170-172° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 10.12 (s, 1H), 9.61 (s, 1H), 8.69 (s, 1H), 8.45 (d, J=9.3 Hz, 1H), 8.23 (d, J=9.3 Hz, 1H); ESIMS m/z 242.3 ([M−H]⁻); IR (thin film) 2238, 1705, 1551, 1314 cm⁻¹.

Example 93: Preparation of 4-(3-Methyl-1H-1,2,4-triazol-1-yl)benzaldehyde (DI53)

To a stirring solution of 4-fluorobenzaldehyde (5.0 g, 40.32 mmol) in DMF (50 mL), were added K₂CO₃ (3.34 g, 40.32 mmol) and 3-methyl-1,2,4-trizole (3.34 g, 40.32 mmol) and the resultant reaction mixture was stirred at RT for 4 h. After completion of the reaction (TLC), the reaction mixture was diluted with water and extracted with EtOAc (3×). The combined EtOAc layer was washed with water and brine then dried over Na₂SO₄ and concentrated under reduced pressure to afforded the title compound as a white solid (4.1 g, 60%): mp 125-128° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.05 (s, 1H), 8.76 (s, 1H), 8.02 (d, 2H), 7.85 (d, 2H), 2.50 (s, 3H); ESIMS m/z 188.04 ([M+H]⁺).

The following compound was made in accordance with the procedures disclosed in Example 93.

4-(1H-1,2,4-triazol-1-yl)-3-(trifluoromethyl)benzaldehyde (DI54)

The title compound was isolated as white solid (1.05 g, 60%): mp 81-83° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.15 (s, 1H), 8.43 (s, 1H), 8.37 (s, 1H), 8.25 (d, J=7.2 Hz, 1H), 8.18 (s, 1H), 7.79 (d, J=7.2 Hz, 1H); ESIMS m/z 241.0 ([M]⁺).

4-(3-Nitro-1H-1,2,4-triazol-1-yl)benzaldehyde (DI55)

The title compound was isolated as pale yellow solid (0.10 g, 23%): mp 159-161° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.10 (s, 1H), 8.89 (s, 1H), 8.15 (m, 2H), 8.00 (m, 2H); ESIMS m/z 217.11 ([M−H]⁻).

3-Bromo-4-(1H-1,2,4-triazol-1-yl)benzaldehyde (DI56)

The title compound was isolated as white solid (3.2 g, 51%): mp 126-128° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.04 (s, 1H), 8.69 (s, 1H), 8.27 (M, 1H, 8.18 (s, 1H) 7.99 (d, J=9.2 Hz, 1H), 7.76 (d, J=9.2 Hz, 1H); ESIMS m/z 250.9 ([M]⁺).

5-Formyl-2-(3-methyl-1H-1,2,4-triazol-1-yl)benzonitrile (DI57)

The title compound was isolated as white solid (0.13 g, 30%): mp 147-149° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.07 (s, 1H), 8.89 (s, 1H), 8.32 (d, J=1.8 Hz, 1H), 8.24 (dd, J=8.6, 1.3 Hz, 1H), 8.06 (d, J=8.6 Hz, 1H), 2.54 (s, 3H); ESIMS m/z 213.09 ([M+H]⁺); IR (thin film) 2239, 1697 cm⁻¹.

3-Nitro-4-(1H-1,2,4-triazol-1-yl)benzaldehyde (DI58)

The title compound was isolated as pale yellow solid (3.0 g, 60%): mp 116-118° C.; ¹H NMR (400 MHz, CDCl₃) δ 10.15 (s, 1H), 8.48 (s, 1H), 8.46 (s, 1H), 8.26 (d, J=6.9 Hz, 1H), 8.16 (s, 1H), 7.83 (d, J=6.9 Hz, 1H); ESIMS m/z 219.00 ([M+H]⁺).

Example 94: Preparation of 1-(4-Vinylphenyl)-1H-1,2,4-triazole (DI59)

To a stirred solution of 4-[1,2,4]triazol-1-yl-benzaldehyde (9.0 g, 52 mmol) in 1,4-dioxane (100 mL), were added K₂CO₃ (10.76 g, 78 mmol) and methyl triphenyl phosphonium bromide (22.2 g, 62.4 mmol) at room temperature. The resultant reaction mixture was heated to 70° C. for 18 h. After completion of the reaction (TLC), the reaction mixture was cooled to room temperature and filtered and the obtained filtrate was concentrated under reduced pressure. Purification by flash chromatography (SiO₂, 100-200 mesh; 25-30% EtOAc in petroleum ether) to afforded the title compound as a white solid (5.6 g, 63%): ESIMS m/z 172.09 ([M+H]⁺).

The following compound was made in accordance with the procedures disclosed in Example 94.

1-(2-Methyl-4-vinylphenyl)-1H-1,2,4-triazole (DI60)

The title compound was isolated as an off white solid (1.5 g, 76%): ¹H NMR (400 MHz, CDCl₃) δ 8.25 (s, 1H), 8.11 (s, 1H), 7.35 (m, 2H), 7.27 (d, J=8.7 Hz, 1H), 6.74 (m, 1H), 5.82 (d, J=17.3 Hz, 1H), 5.36 (d, J=10.0 Hz, 1H), 2.25 (s, 3H); ESIMS m/z 186.14 ([M+H]⁺).

2-(1H-1,2,4-Triazol-1-yl)-5-vinylbenzonitrile (DI61)

The title compound was isolated as an off-white solid (1.40 g, 71%): mp 126-129° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.76 (s, 1H), 8.18 (s, 1H), 7.82-7.84 (m, 1H), 7.72-7.80 (m, 2H), 6.70-6.80 (dd, J=17.6, 10.8 Hz, 1H), 5.90-5.95 (d, J=17.6 Hz, 1H), 5.50-5.70 (d, J=10.8 Hz, 1H); ESIMS m/z 197.03 ([M+H]⁺).

Example 95: Preparation of 2-(3-Nitro-1H-1,2,4-triazol-1-yl)-5-vinylbenzonitrile (DI62)

To a stirred solution of 5-formyl-2-(3-nitro-1H-1,2,4-triazol-1-yl)benzonitrile (0.36 g, 1.49 mmol) in 1,4-dioxane (25 mL), were added K₂CO₃ (0.3 g, 2.2 mmol) and methyl triphenyl phosphonium bromide (0.63 g, 1.79 mmol). The resultant reaction mixture was heated to 100° C. for 18 h. After completion of the reaction (TLC), the reaction mixture was cooled to room temperature and filtered and the obtained filtrate was concentrated under reduced pressure. Purification by flash chromatography (SiO₂, 100-200 mesh; 25-30% EtOAc in petroleum ether) to afford the title compound as a solid (0.25 g, 70%): mp 103-105° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 9.50 (s, 1H), 8.34 (m, 1H), 7.98 (d, J=7.8 Hz, 1H), 7.68 (d, J=7.8 Hz, 1H), 6.87 (m, 1H), 6.20 (d, J=15.7 Hz, 1H), 5.56 (d, J=11.8 Hz, 1H); ESIMS m/z 240.27 ([M−H]⁻); IR (thin film) 2240, 1514, 1312 cm⁻¹.

The following compound was made in accordance with the procedures disclosed in Example 95.

1-(3-Chloro-4-vinylphenyl)-1H-1,2,4-triazole (DI63)

The title compound was isolated as an off-white solid (2.3 g, 80%): mp 134-137° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.56 (s, 1H), 8.11 (s, 1H), 7.76 (s, 1H), 7.70 (d, J=9.0 Hz, 1H), 7.57 (d, J=9.0 Hz, 1H), 7.10 (m, 1H), 5.80 (d, J=17.2 Hz, 1H), 5.47 (d, J=12.4 Hz, 1H); ESIMS m/z 206.04 ([M+H]⁺.

3-Methyl-1-(4-vinylphenyl)-1H-1,2,4-triazole (DI64)

The title compound was isolated as a white solid (0.6 g, 60%): mp 109-111° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.42 (s, 1H), 7.40-7.60 (m, 4H), 6.70-7.00 (dd, J=17.6, 10.8 Hz, 1H), 5.80 (d, J=17.6 Hz, 1H), 5.30 (d, J=17.6 Hz, 1H), 2.50 (s, 3H); ESIMS m/z 186.20 ([M+H]⁺).

1-(2-(Trifluoromethyl)-4-vinylphenyl)-1H-1,2,4-triazole (DI65)

The title compound was isolated as a colorless oil (0.6 g, 60%): ¹H NMR (400 MHz, CDCl₃) δ 8.32 (s, 1H), 8.14 (s, 1H), 7.84 (s, 1H), 7.72 (d, J=8.0 Hz, 1H), 7.50 (d, J=7.6 Hz, 1H), 6.70-6.90 (dd, J=17.6, 10.8 Hz, 1H), 5.90-6.00 (d, J=17.6 Hz, 1H), 5.50-5.80 (d, J=10.8 Hz 1H); ESIMS m/z 240.16 ([M+H]⁺).

3-Nitro-1-(4-vinylphenyl)-1H-1,2,4-triazole (DI66)

The title compound was isolated as a pale yellow solid (61 mg, 20%): mp 137-139° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.60 (s, 1H), 7.68 (d, J=7.7 Hz, 2H), 7.60 (d, J=8.3 Hz, 2H), 6.77 (dd, J=17.7, 10.8, 1H), 5.87 (d, J=17.7 Hz, 1H), 5.42 (d, J=10.8 Hz, 1H); ESIMS m/z 217.28 ([M+H]⁺).

1-(2-Bromo-4-vinylphenyl)-1H-1,2,4-triazole (DI67)

The title compound was isolated as a white solid (1.2 g, 40%): mp 75-77° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.48 (s, 1H), 8.12 (s, 1H), 7.75 (s, 1H) 7.42 (s, 2H), 6.70 (m, 1H), 5.83 (d, J=18 Hz, 1H), 5.42 (d, J=12 Hz, 1H); ESIMS m/z 249.1 ([M]⁺).

2-(3-Methyl-1H-1,2,4-triazol-1-yl)-5-vinylbenzonitrile (DI68)

The title compound was isolated as an off-white solid (0.6 g, 60%): mp 96-97° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.66 (s, 1H), 7.80 (s, 1H), 7.74 (m, 2H), 6.73 (dd, J=17.6 Hz, 10.8 Hz, 1H), 5.88 (d, J=17.6 Hz, 1H), 5.49 (d, J=10.8 Hz, 1H), 2.52 (s, 3H); ESIMS m/z 211.10 ([M+H]⁺); IR (thin film) 2229 cm⁻¹.

1-(2-Nitro-4-vinylphenyl)-1H-1,2,4-triazole (DI69)

The title compound was isolated as a yellow solid (1.78 g, 60%): mp 102-104° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.40 (s, 1H), 8.12 (s, 1H), 8.02 (s, 1H), 7.72-7.76 (d, J=8.0 Hz, 1H), 7.52-7.56 (d, J=17.6 Hz, 1H), 6.70-6.82 (dd, J=17.6, 10.8 Hz, 1H), 5.85-6.00 (d, J=17.6 Hz, 1H), 5.50-5.60 (d, J=10.8, Hz 1H); ESIMS m/z 217.0 ([M+H]⁺).

Example 96: Preparation of 3-Methyl-2-(1H-1,2,4-triazol-1-yl)-5-vinylbenzonitrile (DI70)

Step 1. 5-Bromo-2-fluoro-3-methylbenzaldehyde

To a stirred solution of di-isopropyl amine (4.01 g, 39.88 mmol) in THF (20 mL) was added n-butyl lithium (1.6 M in hexane) (19.9 mL, 31.91 mmol) at −78° C. slowly dropwise over the period of 10 min, the reaction mixture was stirred at −78° C. for 30 min. A solution of 4-bromo-1-fluoro-2-methylbenzene (5.0 g, 26.6 mmol) in THF (30.0 mL) was added at −78° C., and the reaction mixture was stirred for 1 h at the same temperature. DMF (5.0 mL) was added and stirred at −78° C. for another 30 min. The reaction was monitored by TLC; then the reaction mixture was quenched with 1N HCl solution (aq) at 0° C. The aqueous layer was extracted with diethyl ether, washed with water and saturated brine solution. The combined organic layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to obtain the crude compound purified by flash column chromatography (SiO₂, 100-200 mesh; eluting with 5% ethyl acetate/pet ether) to afford the title compound as a white solid (3.6 g, 64%); mp 48-50° C.: ¹H NMR (400 MHz, CDCl₃) δ 8.33 (s, 1H), 8.22 (s, 1H), 7.67 (s, 1H), 7.60 (s, 1H), 6.75 (dd, J=17.6, 10.8 Hz, 1H), 5.92 (dd, J=17.6, 10.8 Hz, 1H), 5.52 (d, J=17.6 Hz, 1H), 2.21 (s, 3H); ESIMS m/z 211.35 ([M−H]⁻).

Step 2. ((E)-5-Bromo-2-fluoro-3-methylbenzaldehyde oxime

To a stirred solution of 5-bromo-2-fluoro-3-methylbenzaldehyde (3.5 g, 16.2 mmol) in ethanol (50.0 mL) were added sodium acetate (2.0 g, 24.3 mmol) and hydroxylamine hydrochloride (1.69 g, 24.3 mmol) at RT. The reaction mixture was stirred at RT for 3 h. The reaction mixture was concentrated on rotavapour to obtain crude compound, which was washed with water filtered and dried under vacuum to afford the title compound as a white solid: mp 126-127° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.32 (s, 1H), 7.73 (d, J=2.4 Hz, 1H), 7.51 (s, 1H), 7.34 (d, J=2.4 Hz, 1H), 2.25 (s, 3H); ESIMS m/z 232.10 ([M+H]⁺).

Step 3. 5-Bromo-2-fluoro-3-methylbenzonitrile

A stirred solution of (E)-5-bromo-2-fluoro-3-methylbenzaldehyde oxime (0.5 g, 2.2 mmol) in acetic anhydride (5.0 mL) was heated to reflux for 18 h. The reaction mixture was diluted with water and extracted with ethyl acetate. The combined ethyl acetate layer was washed with brine and dried over Na₂SO₄ and concentrated under reduced pressure to afford the crude compound as a light brown gummy material (0.4 g, crude): ESIMS m/z 213.82 ([M+H]⁺).

Step 4. 5-Bromo-3-methyl-2-(1H-1,2,4-triazol-1-yl)benzonitrile (DI71)

To a stirred solution of 5-bromo-2-fluoro-3-methylbenzonitrile (1.0 g, 47.716 mmol), in DMF (10.0 mL) was added potassium carbonate (1.95 g, 14.14 mmol) followed by 1H-1,2,4-triazole (0.811 g, 9.433 mmol) at RT. The reaction mixture was heated to 140° C. for 18 h. The reaction mixture was cooled to RT, diluted with water and extracted with ethyl acetate (2×100 mL). The combined ethyl acetate layer was washed with brine and dried over Na₂SO₄ and concentrated under reduced pressure to afford the crude compound purified by flash column chromatography (SiO₂, 100-200 mesh; eluting with 30% ethyl acetate/pet ether) to afford the title compound as a pink solid (0.6 g, 49%): ¹H NMR (400 MHz, CDCl₃) δ 8.39 (s, 1H), 8.23 (s, 1H), 7.91 (d, J=2.4 Hz, 2H), 2.21 (s, 3H), ESIMS m/z 262.57 ([M+H]⁺); IR (thin film) 2231, 554 cm⁻¹.

Step 5. 3-Methyl-2-(1H-1,2,4-triazol-1-yl)-5-vinylbenzonitrile (DI70)

A mixture of 5-bromo-3-methyl-2-(1H-1,2,4-triazol-1-yl)benzonitrile (0.6 g, 2.3 mmol), potassium carbonate (0.95 g, 6.87 mmol), vinyl boronic anhydride (0.82 g, 3.43 mmol) and triphenylphosphine (0.13 g, 0.114 mmol) in toluene (20.0 mL) were stirred and degassed with argon for 30 min. The reaction mixture was heated to reflux for 18 h. The reaction mixture was cooled to RT, diluted with water and extracted with ethyl acetate (2×100 mL). The combined ethyl acetate layer was washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure to afford the crude compound that was purified by flash column chromatography (SiO₂, 100-200 mesh; eluting with 30% ethyl acetate/pet ether) to afford the title compound as a pink solid (0.25 g, 52%): ¹H NMR (400 MHz, CDCl₃) δ 8.33 (s, 1H), 8.22 (s, 1H), 7.67 (s, 1H), 7.60 (s, 1H), 6.75 (dd, J=17.6, 10.8 Hz, 1H), 5.92 (d, J=17.6, 1H), 5.52 (d, J=10.8 Hz, 1H), 2.21 (s, 3H), ESIMS m/z 211.35 ([M+H]⁺); IR (thin film) 2236, 1511 cm⁻¹.

The following compound was made in accordance with the procedures disclosed in Steps 4 and 5 of Example 96.

1-(2-Fluoro-4-vinylphenyl)-1H-1,2,4-triazole (DI72)

1-(4-Bromo-2-fluorophenyl)-1H-1,2,4-triazole (DI73) was isolated as a pale yellow solid (3.0 g, 75%): mp 113-116° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.69 (s, 1H), 8.13 (m, 2H), 7.50 (m, 1H), 7.21 (m, 1H); ESIMS m/z 241.93 ([M]⁺). The title compound (DI72) was isolated as a yellow solid (1.0 g, 71%): mp 67-70° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.67 (s, 1H), 8.13 (s, 1H), 7.94 (m, 1H), 7.41 (m, 1H), 7.24 (s, 1H), 6.75 (dd, J=17.6, 10.8 Hz, 1H), 5.81 (d, J=17.6 Hz, 1H), 5.37 (d, J=10.8 Hz, 1H); ESIMS m/z 190.00 ([M+H]⁺).

Example 119: Preparation of 1-(1-(4-Vinylphenyl)-1H-1,2,4-triazol-5-yl)ethanone (DI78)

To a stirred solution of 1-(4-vinyl-phenyl)-1H-[1,2,4]triazole (1 g, 5.8 mmol) in 25 mL of THF, was added n-BuLi (0.37 g, 5.8 mmol) at −78° C. and stirred for 30 min. To this N-methoxy-N-methyl acetamide in THF (0.66 g, 6.4 mmol) was added and the resultant reaction mixture was stirred at RT for 16 h. The reaction mixture was quenched with a saturated aqueous NH₄Cl solution and extracted with EtOAc (3×50 mL). The combined EtOAc layer was washed with brine and dried over sodium sulphate and concentrated under reduced pressure. The crude compound was purified by flash chromatography (SiO₂, 100-200 mesh, 40% EtOAc in Pet ether) to afford the title compound as an off white solid (280 mg, 23%): mp 97-98° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.10 (s, 1H), 7.50 (d, 2H), 7.38 (d, 2H), 6.68 (dd, 1H), 5.85 (d, 1H), 5.38 (d, 1H), 2.75 (s, 3H); ESIMS m/z 214.14 ([M+H]⁺).

Example 120: Preparation of Cyclopropyl(1-(4-vinylphenyl)-1H-1,2,4-triazol-5-yl)methanone (DI79)

To a stirred solution of 1-(4-vinyl-phenyl)-1H-[1,2,4]triazole (1 g, 5.8 mmol) in 25 mL of THF, was added n-BuLi (0.37 g, 5.8 mmol) at −78° C. and stirred for 30 min. To this N-methoxy N-methylcyclopropoxide in THF (0.82 g, 6.4 mmol) was added and the resultant reaction mixture was stirred at RT for 16 h. The reaction mixture was quenched with a saturated aqueous NH₄Cl solution and extracted with EtOAc (3×25 mL). The combined EtOAc layer was washed with brine and dried over sodium sulphate and concentrated under reduced pressure. The crude compound was purified by flash chromatography (SiO₂, 100-200 mesh, 40% EtOAc in Pet ether) to afford the title compound as an off white solid (420 mg, 30%): mp 90-91° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.12 (s, 1H), 7.50 (d, J=7.8 Hz, 2H), 7.38 (d, J=7.8 Hz, 2H), 6.75 (dd, J=16.3, 10.7 Hz, 1H), 5.81 (d, J=16.3 Hz, 1H), 5.35 (d, J=10.7 Hz, 1H), 3.22 (m, 1H), 1.27 (m, 2H), 1.18 (m, 2H); ESIMS m/z 240.18 ([M+H]⁺); IR (thin film) 2922, 1630 cm⁻¹.

Example 121: Preparation of 5-(Methylthio)-1-(4-vinylphenyl)-1H-1,2,4-triazole (DI80)

To a stirred solution of 1-(4-vinyl-phenyl)-1H-[1,2,4]triazole (1 g, 5.8 mmol) in 50 mL of THF, was added n-BuLi (0.41 g, 6.4 mmol) at −78° C. and stirred for 30 min. To this dimethyldisulfide in THF (0.6 g, 6.43 mmol) was added and the resultant reaction mixture was stirred at RT for 16 h. The reaction mixture was quenched with a saturated aqueous NH₄Cl solution and extracted with EtOAc (3×25 mL). The combined EtOAc layer was washed with brine and dried over sodium sulphate and concentrated under reduced pressure. The crude compound was purified by flash chromatography (SiO₂, 100-200 mesh, 40% EtOAc in Pet ether) to afford the title compound as an off white solid (0.6 g, 48%): mp 68-70° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.96 (s, 1H), 7.05 (m, 4H), 6.75 (dd, J=16.4, 10.7 Hz, 1H), 5.81 (d, J=16.4 Hz, 1H), 5.35 (d, J=10.7 Hz, 1H), 2.73 (s, 3H); ESIMS m/z 218.09 ([M+H]⁺).

Example 122: Preparation of 5-Methyl-1-(4-vinylphenyl)-1H-1,2,4-triazole (DI81)

To a stirred solution of 1-(4-vinyl-phenyl)-1H-[1,2,4]triazole (0.5 g, 2.9 mmol) in 10 mL of THF, was added n-BuLi (0.22 g, 3.5 mmol) at −78° C. and stirred for 30 min. To this methyl iodide in THF (0.50 g, 3.5 mmol) was added and the resultant reaction mixture was stirred at RT for 16 h. The reaction mixture was quenched with a saturated aqueous NH₄Cl solution and extracted with EtOAc (3×25 mL). The combined EtOAc layer was washed with brine and dried over sodium sulphate and concentrated under reduced pressure The crude compound was purified by flash chromatography (SiO₂, 100-200 mesh, 40% EtOAc in Pet ether) afford the title compound as a pale brown liquid (250 mg, 46%): ¹H NMR (400 MHz, CDCl₃) δ 7.93 (s, 1H), 7.55 (d, J=9 Hz, 2H), 7.42 (d, J=9 Hz, 2H), 6.76 (dd, J=18, 11 Hz, 1H), 5.83 (d, J=18 Hz, 1H), 5.38 (d, J=11 Hz, 1H), 2.55 (s, 3H); ESIMS m/z 186.13 ([M+H]⁺); IR (thin film) 1517, 1386, 1182, 847 cm⁻¹.

Example 97: Preparation of (E)-1-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)phenyl)-1H-1,2,4-triazole (DC1)

To a stirred solution of 1-(1-bromo-2,2,2-trifluoro-ethyl)-3,5-dichloro-benzene (2.0 g, 6.51 mmol) in 1,2-dichlorobenzene (25 mL), were added 1-(4-vinyl-phenyl)-1H-[1,2,4]triazole (2.22 g, 13.0 mmol), CuCl (64 mg, 0.65 mmol) and 2,2-bipyridyl (0.2 g, 1.3 mmol). The resultant reaction mixture was degassed with argon for 30 min, then stirred at 180° C. for 24 h. After completion of reaction (TLC), the reaction mixture was cooled to RT and filtered and the filtrate concentrated under reduced pressure. Purification by flash chromatography (SiO₂, 100-200 mesh; 25-30% EtOAc in petroleum ether) afforded the title compound as an off-white solid (0.8 g, 32%): mp 93-97° C.; ¹H NMR (300 MHz, CDCl₃) δ 8.56 (s, 1H), 8.11 (s, 1H), 7.68 (d, J=8.4 Hz, 2H), 7.54 (d, J=8.4 Hz, 2H), 7.38 (t, J=1.8 Hz, 1H), 7.29 (s, 2H), 6.62 (d, J=15.6 Hz, 1H), 6.42 (dd, J=15.6, 8.2 Hz, 1H), 4.15 (m, 1H); ESIMS m/z 398.05 ([M+H]⁺).

Compounds DC2-DC37, DC44, DC45, DC47-49, DC50, DC51, DC54, DC58, DC60, DC62, and DC63-DC67 in Table 1 were made in accordance with the procedures disclosed in Example 97.

Example 98: Preparation of (E)-2-(3-Nitro-1H-1,2,4-triazol-1-yl)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzonitrile (DC40)

To a stirred solution of 2-(3-nitro-1H-1,2,4-triazol-1-yl)-5-vinylbenzonitrile (0.9 g, 3.7 mmol) in 1,2-dichlorobenzene (10 mL), were added 5-(1-bromo-2,2,2-trifluoroethyl)-1,2,3-trichlorobenzene (2.5 g, 7.5 mmol), CuCl (73 mg, 0.74 mmol) and 2,2-bipyridyl (0.23 g, 1.49 mmol) and the resultant reaction mixture was degassed with argon for 30 min and then stirred at 180° C. for 14 h. After completion of the reaction (TLC), the reaction mixture was cooled to RT and filtered and the filtrate was concentrated under reduced pressure. Purification by flash chromatography (SiO₂, 100-200 mesh, 25-30% EtOAc in Pet ether) afforded the title compound as an off white solid (0.9 g, 50%): mp 70-73° C.; ¹H NMR (300 MHz, CDCl₃) δ 8.86 (s, 1H), 7.88 (m, 3H), 7.44 (s, 2H), 6.67 (d, J=16.0 Hz, 1H), 6.56 (dd, J=16.0, 7.6 Hz, 1H), 4.19 (m, 1H); ESIMS m/z 436.11 ([M−2H]⁻).

Example 99: Preparation of (E)-2-(3-Amino-1H-1,2,4-triazol-1-yl)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzonitrile (DC41)

To a stirred solution of (E)-2-(3-nitro-1H-1,2,4-triazol-1-yl)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzonitrile (0.6 g, 1.2 mmol) in MeOH (10 mL), were added Zn dust (0.39 g, 5.98 mmol) and sat. aq NH₄Cl solution (5 mL) and the resultant reaction mixture was stirred at RT for 2 h. After completion of the reaction (TLC), the reaction mass was concentrated under reduced pressure. The reaction mass was diluted with DCM, filtered through a celite bed, and the obtained filtrate concentrated under reduced pressure to afford the title compound as a solid (0.5 g, 89%): mp 72-75° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 8.72 (s, 1H), 8.26 (s, 1H), 8.01 (d, J=8.4 Hz, 1H), 7.91 (s, 2H), 7.77 (d, J=8.4 Hz, 1H), 6.42 (dd, J=15.6, 9.2 Hz, 1H), 6.83 (d, J=15.6 Hz, 1H), 5.87 (s, 2H), 4.89 (m, 1H); ESIMS m/z 469.95 ([M−H]⁻).

Compound DC38 in Table 1 was made in accordance with the procedures disclosed in Example 99. Also, compound DC55 in Table 1 was made from compound DC54 in accordance with the procedures disclosed in Example 99, with the exception of using ammonium formate in place of ammonium chloride.

Example 100: Preparation of (E)-N-(1-(2-Cyano-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)-1H-1,2,4-triazol-3-yl)-N-(cyclopropanecarbonyl)cyclopropanecarboxamide (DC42)

To a stirred solution of (E)-2-(3-amino-1H-1,2,4-triazol-1-yl)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzonitrile (0.1 g, 0.21 mmol) in DCM at RT, was added cyclopropylcarbonyl chloride (0.045 g, 0.42 mmol) and the reaction mixture was stirred for 2 h at RT. The reaction mixture was diluted with DCM and washed with water and brine and dried over Na₂SO₄. Concentration under reduced pressure and purification by preparative HPLC afforded the title compound as a solid (0.09 g, 79%): mp 104-107° C.; ¹H NMR (300 MHz, CDCl₃) δ 8.78 (s, 2H), 7.83 (s, 1H), 7.80 (m, 2H), 7.42 (s, 2H), 6.65 (d, J=16.4 Hz, 1H), 6.51 (dd, J=7.6, 8.0 Hz, 1H), 4.17 (m, 1H), 2.16 (m, 2H), 1.25 (m, 4H), 1.00 (m, 4H); ESIMS m/z 609.98 ([M+H]⁺); IR (thin film) 2234, 1714, 1114, 807 cm⁻¹.

Example 101: Preparation of (E)-N-(1-(2-Cyano-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)phenyl)-1H-1,2,4-triazol-3-yl)cyclopropanecarboxamide (DC43)

To a stirred solution of (E)-2-(3-amino-1H-1,2,4-triazol-1-yl)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzonitrile (0.15 g, 0.31 mmol) in DCM at 0° C., were added triethylamine (0.1 g, 1 mmol) and cyclopropylcarbonyl chloride (0.04 g, 0.38 mmol) and the reaction mixture was stirred for 1 h at 0° C. The reaction mixture was diluted with DCM and washed with water and brine and dried over Na₂SO₄. Concentration under reduced pressure and purification by column chromatography (SiO₂, 100-200 mesh) afforded the title compound as a solid (66 mg, 34%): mp 109-112° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 10.94 (br s, 1H), 8.36 (s, 1H), 8.08 (m, J=8.4 Hz, 1H), 7.91 (s, 2H), 7.84 (d, J=8.4 Hz, 1H), 7.13 (dd, J=15.6, 9.2 Hz, 1H), 6.87 (d, J=15.6 Hz, 1H), 4.92 (m, 1H), 1.99 (br s, 1H), 0.82 (s, 4H); ESIMS m/z 540.04 ([M+H]⁺); IR (thin film) 3233, 2233, 1699, 1114, 807 cm⁻¹.

Compound DC39 in Table 1 was made in accordance with the procedures disclosed in Example 101.

Example 102: Preparation of 1-(4-(1H-1,2,4-triazol-1-yl)phenyl)ethanone (DI74)

To a stirred solution of 4-bromoacetophenone (10 g, 50 mmol) in DMF (100 mL), were added 1,2,4-triazole (5 g, 75 mmol), Cs₂CO₃ (32.6 g, 100.5 mmol) and CuI (1.4 g, 10.1 mmol) and the resultant reaction mixture was refluxed for 48 h. After completion of the reaction (by TLC), the reaction mixture was cooled to RT and diluted with water (200 mL) and extracted with EtOAc. The combined organic layer was washed with brine and dried over Na₂SO₄ and concentrated under reduced pressure. Purification by washing with diethyl ether afforded the title compound as a solid (5 g, 96%): ¹H NMR (400 MHz, CDCl₃) δ 8.71 (s, 1H), 8.16, (s, 1H), 8.13 (d, J=8.6 Hz, 2H), 7.83 (d, J=8.6 Hz, 2H), 2.66 (s, 3H); ESIMS m/z 186.02 ([M−H]⁻).

Example 103: Preparation of 1-(4-(1H-1,2,4-triazol-1-yl)phenyl)-3-(3,5-dichlorophenyl)-4,4,4-trifluorobutan-1-one (DI75)

Step 1. 1-(4-(1-(Trimethylsilyloxy)vinyl)phenyl)-1H-1,2,4-triazole (DI76)

To a stirred solution of 1-(4-(1H-1,2,4-triazol-1-yl)phenyl)ethanone (4.5 g, 24.0 mmol) in DCM at 0° C., were added TEA (3.7 g, 36.1 mmol) and trimethylsilyl triflluoromethanesulfonate (8 g, 36 mmol) and the resultant reaction mixture was stirred for 1 h. The reaction mixture was quenched with a mixture of sat aq sodium bicarbonate solution and ether. The ether layer and was separated, washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure to afford the title compound (5.5 g) which was taken directly to next step.

Step 2. 1-(4-(1H-1,2,4-triazol-1-yl)phenyl)-3-(3,5-dichlorophenyl)-4,4,4-trifluorobutan-1-one (DI75)

To a stirred solution of 1-(4-(1-(trimethylsilyloxy)vinyl)phenyl)-1H-1,2,4-triazole (6 g, 23 mmol) and 1-(1-bromo-2,2,2-trifluoro-ethyl)-3,5-dichlorobenzene (7.1 g, 34.7 mmol) in 1,2-dichlorobenzene (30 mL) was degassed with argon. To this CuCl (0.23 g, 2.31 mmol) and 2,2-bipyridyl (0.73 g, 4.63 mmol) was added to the above reaction mixture and the resultant reaction mixture was heated to 180° C. for 18 h. After completion of the reaction (by TLC), the reaction mixture was absorbed onto silica gel and purified by column chromatography (SiO2; 10% EtOAc in petroleum ether) to afford title compound as a solid (3 g, 31%): ¹H NMR (400 MHz, CDCl₃) δ 8.67 (s, 1H), 8.15 (s, 1H), 8.10 (d, J=8.3 Hz, 2H), 7.82 (d, J=8.3 Hz, 2H), 7.33 (m, 1H), 7.30 (m, 2H), 4.20 (m, 1H), 3.63 (m, 2H); ESIMS m/z 412. 14 ([M−H]⁻).

Example 104: Preparation of 2-(4-(1H-1,2,4-triazol-1-yl)phenyl)-4-(3,5-dichlorophenyl)-5,5,5-trifluoropentan-2-ol (DI77)

To a solution of 1-(4-(1H-1,2,4-triazol-1-yl)phenyl)-3-(3,5-dichlorophenyl)-4,4,4-trifluorobutan-1-one (300 mg, 0.726 mmol) in THF cooled to 0° C. was added methylmagnesium bromide (450 mg, 5 mmol) drop wise. The reaction was stirred for 3 h at 0° C., then the reaction mixture was quenched with sat aq NH₄Cl solution and extracted with ethyl acetate. The combined EtOAc layer was washed with water and brine, dried over Na₂SO₄ and concentrated under reduced pressure. Purification by column chromatography (SiO₂, 100-200 mesh; 20%-25% EtOAc in petroleum ether) afforded the title compound as a solid (100 mg, 32%): ¹H NMR (400 MHz, CDCl₃) δ two diastereoisomers 8.58 (s, 1H, minor), 8.48 (s, 1H, major), 8.13 (s, 1H, minor), 8.09 (s, 1H, major), 7.70 (d, J=9.0 Hz, 2H, minor), 7.53 (d, J=9.0 Hz, 2H, minor), 7.40 (d, J=9.0 Hz, 2H, major), 7.31 (m, 1H, minor), 7.27 (d, J=9.0 Hz, 2H, major), 7.20 (m, 2H, minor), 7.01 (m, 1H, major), 6.75 (m, 2H, major), 350 (m, 1H), 2.50 (m, 2H), 1.56 (s, 3H, major), 1.54 (s, 3H, minor); ESIMS m/z 430.05 ([M+H]⁺).

Example 105: Preparation of (E)-1-(4-(4-(3,5-Dichlorophenyl)-5,5,5-trifluoropent-2-en-2-yl)phenyl)-1H-1,2,4-triazole (DC68)

To a solution of 2-(4-(1H-1,2,4-triazol-1-yl)phenyl)-4-(3,5-dichlorophenyl)-5,5,5-trifluoropentan-2-ol (100 mg, 0.233 mmol) in toluene was added a catalytic amount of p-toluenesulfonic acid (PTSA) and the water was removed by azeotropic distillation over the course of 12 h. The reaction mixture was cooled to room temperature and dissolved in ethyl acetate. The solution was washed with sat aq NaHCO₃ solution and brine, dried over Na₂SO₄ and concentrated under reduced pressure. Purification by column chromatography (SiO₂, 100-200 mesh; 20%-25% EtOAc in petroleum ether) afforded the title compound as a solid (30 mg, 31%).

Example 123: Preparation of (E)-5-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(1H-1,2,4-triazol-1-yl)benzaldehyde (DC52)

To a stirred solution of (E)-5-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(1H-1,2,4-triazol-1-yl)benzonitrile (0.3 g, 0.71 mmol) in toluene (10 mL) at −78° C. was added dropwise diisobutylaluminum hydride (DIBAL-H, 1.0 M solution in toluene; 0.85 mL), and the reaction mixture was stirred at −78° C. for 20 min. The reaction mixture was quenched with the addition of 1 N HCl solution, then the aqueous layer was extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure. The crude compound was purified by flash column chromatography (SiO₂; 50% EtOAc/Pet ether) to afford the title compound as a yellow oil.

Compound DC53 in Table 1 was made in accordance with the procedures disclosed in Example 123.

Example 124: Preparation of (E)-5-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N-methyl-2-(1H-1,2,4-triazol-1-yl)aniline (DC57)

To a stirred solution of (E)-5-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(1H-1,2,4-triazol-1-yl)aniline (0.3 g, 0.7 mmol) in DCM (10 mL) was added triethylamine (0.155 mL, 1.09 mmol) and methyl iodide (0.124 g, 0.873 mmol). The reaction was stirred at RT for 18 h. The DCM layer was washed with water and brine, dried over Na₂SO₄ and concentrated under reduced pressure. The crude compound was purified by flash column chromatography (SiO₂; 50% EtOAc/Pet ether) to afford the title compound as a yellow semi-solid (0.07 g, 70%).

Example 125: Preparation of (E)-5-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(1H-1,2,4-triazol-1-yl)benzoic acid (DC61)

A solution of (E)-ethyl 5-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(1H-1,2,4-triazol-1-ylbenzoate (0.2 g, 0.4 mmol) in 6 N HCl (10 mL) was stirred at 100° C. for 18 h. The reaction was cooled to RT, resulting in a white solid precipitate. The precipitate was filtered to afford the title compound as a white solid (0.12 g, 60%).

Example 126: Preparation of (Z)-5-((E)-3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-N′-hydroxy-2-(1H-1,2,4-triazol-1-yl)benzimidamide (DC59)

A solution of (E)-5-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-en-1-yl)-2-(1H-1,2,4-triazol-1-yl)benzonitrile (0.3 g, 0.71 mmol), sodium acetate (0.087 g, 1.065 mmol) and hydroxylammonium chloride (0.072 g, 1.065 mmol) in 9:1 ethanol/water mixture (10 mL) was stirred at 70° C. for 8 h. The reaction was cooled to RT, and the ethanol was evaporated. The residue was dissolved in water and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over Na₂SO₄ and concentrated under reduced pressure to afford the title compound as an off white solid.

Example 127: Preparation of (E)-1-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluoro-3-methoxybut-1-en-1-yl)phenyl)-1H-1,2,4-triazole (DC70)

Step 1. (E)-3-(4-(1H-1,2,4-triazol-1-yl)phenyl)-1-(3,5-dichlorophenyl)prop-2-en-1-one

To a solution of 1-(3,5-dichlorophenyl)ethanone (0.5 g, 2.6 mmol) in ethanol (20 mL) was added 4-(1H-1,2,4-triazol-1-yl)benzaldehyde (0.46 g, 2.65 mmol) and the reaction was cooled to 0° C. Sodium hydroxide (0.22 g, 5.29 mmol) in water (10 mL) was then added and the reaction was allowed to stir for 2 h at 0° C. The reaction was extracted with EtOAc and the combined organic layers were dried over Na₂SO₄ and concentrated under reduced pressure to afford the title compound (0.149 g, 17%):); ESIMS m/z 430.05 ([M+H]⁺) 344.08

Step 2. (E)-4-(4-(1H-1,2,4-triazol-1-yl)phenyl-2-(3,5-dichlorophenyl)-1,1,1-trifluorobut-3-en-2-ol (DC69)

To a solution of (E)-3-(4-(1H-1,2,4-triazol-1-yl)phenyl)-1-(3,5-dichlorophenyl)prop-2-en-1-one (1 g, 3 mmol) in THF (150 mL) was added trifluoromethyltrimethylsilane (0.517 g, 3.644 mmol) and tetra-n-butylammonium fluoride (TBAF) (1.0 M, 1 mL) at 0° C. The reaction was slowly warmed to RT and allowed to stir for 2 h. The reaction was then cooled to 0° C. and 5 M HCl solution was added and the reaction was stirred for an additional 4 h at RT. The reaction was extracted with DCM and the combined organic layers were dried over Na₂SO₄ and concentrated under reduced pressure. The crude compound was purified by flash column chromatography (SiO₂; 25% EtOAc/hexanes) to afford the title compound as an off-white solid (0.3 g, 25%).

Step 3. (E)-1-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluoro-3-methoxybut-1-en-1-yl)phenyl)-1H-1,2,4-triazole (DC70)

To a solution of (E)-4-(4-(1H-1,2,4-triazol-1-yl)phenyl)-2-(3,5-dichlorophenyl)-1,1,1-trifluorobut-3-en-2-ol (0.15 g, 0.36 mmol) in THF (5 mL) was added NaH (60%, 10 mg, 0.44 mmol) at 0° C. The reaction was allowed to stir at 0° C. for 30 min, then methyl iodide (61 mg, 0.44 mmol) was added slowly and the reaction was warmed to RT and allowed to stir for 4 h. The reaction was quenched with aq NH₄Cl solution and extracted with DCM. The combined organic layers were dried over Na₂SO₄ and concentrated under reduced pressure to afford the title compound as an off-white solid (55 mg, 35%).

Example 128: Preparation of (E)-2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-N-(1-(2,2,2-trifluoroethylcarbamoyl)cyclopropyl)benzamide (F1)

To a stirred solution of (E)-2-chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic acid (300 mg, 0.67 mmol) and 1-amino-N-(2,2,2-trifluoroethyl)cyclopropanecarboxamide (148 mg, 0.81 mmol) in DCM/DMF (5 mL, 1:1), 2-chloro-1,3-dimethylimidazolidinium hexafluorophosphate (CIP) (92 mg, 0.33 mmol), 1-hydroxy-7-azabenzotriazole (HOAt) (48 mg, 0.33 mmol) and DMAP (5 mol %) were added, and the resulting mixture was stirred at room temperature (RT) for 4 h. The reaction mixture was poured into ice-water and extracted with EtOAc. The organic phase was dried (Na₂SO₄), filtered, concentrated and the residue was purified by column chromatography on silica (100-200 mesh) eluting with 30% EtOAc in petroleum ether to give the title compound as pale yellow gum (300 mg, 75%). Characterization data for this molecule is listed in Table 2.

Example 129: Preparation of (E)-2-Bromo-N-(1-cyanocyclopropyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamide (F7)

To a stirred solution of (E)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoic acid (100 mg, 0.205 mmol) in DCE (10.0 mL) at RT was added 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC hydrochloride) (58.9 mg, 0.307 mmol), 1-amino-1-cyclopropanecarbonitrile hydrochloride (24.3 mg, 0.296 mmol), DMAP (catalytic) and TEA (22.79 mg, 0.225 mmol). The resulting reaction mixture was stirred at RT for 18 h. To the reaction mixture was added EtOAc (50 mL) and 0.1N HCl (10 mL) and the layers were separated. The aqueous layer was extracted with EtOAc (1×). The combined organic layers were washed with aq NaHCO₃ (1×), dried (MgSO₄), filtered and concentrated under reduce pressure to give an oil. Purification by flash chromatography (SiO₂, 230-400 mesh; eluting with 35% EtOAc in hexanes) afforded the title compound as a white solid (13 mg, 11.5%). Characterization data for this molecule is listed in Table 2.

Example 130: Preparation of tert-Butyl (14(2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-carbamate

To a stirred solution of 1-((tert-butoxycarbonyl)amino)cyclopropanecarboxylic acid (10.0 g, 49.7 mmol) in CH₂Cl₂ (80 mL) was added EDC.HCl (13.8 g, 71.8 mmol) followed by 2,2,2-trifluoroethylamine (8.21 g, 82.8 mmol) and 4-(dimethylamino)pyridine (7.31 g, 59.8 mmol). The reaction mixture was stirred at ambient temperature for 18 h, taken up in 300 mL of EtOAC, then washed with aq. 10% HCl (3×), aq. 10% K₂CO₃ (2×) and aq. sat. NaCl (1×). The organic phase was dried (MgSO₄) and concentrated in vacuo to afford the title compound as a white solid (11.8 g, 84%): mp 166-167° C.; ¹H NMR (400 MHz, DMSO-d₆) rotamers δ 8.43 (s, 0.3H), 8.20 (s, 0.7H), 7.41 (s, 0.7H), 7.11 (s, 0.3H), 3.84 (dt, J=9.9, 4.9 Hz, 2H), 1.38 (d, J=11.4 Hz, 9H), 1.24 (q, J=4.3 Hz, 2H), 0.92 (q, J=4.3 Hz, 2H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −70.57; ¹³C NMR (101 MHz, DMSO-d₆) rotamers δ 172.82, 155.37, 124.64 (q, J=281 Hz), 78.29, 40.18 (q, J=34 Hz), 35.43, 34.70, 28.05, 27.84, 17.28, 16.62.

The following molecules was made in accordance with the procedure disclosed in Example 130:

tert-Butyl (1-((2,2,2-Trifluoroethyl)carbamoyl)cyclobutyl)carbamate

The title molecule was isolated as a white solid (1.94, 28%): mp=185-188° C.; ¹H NMR (400 MHz, DMSO-d₆) rotomers δ 8.06 (s, 0.3H), 7.96 (d, J=7.0 Hz, 0.7H), 7.44 (s, 0.7H), 7.11 (s, 0.3H), 3.83 (qd, J=9.7, 6.4 Hz, 2H), 2.40 (dtd, J=12.1, 5.9, 2.5 Hz, 2H), 2.03 (ddd, J=12.1, 9.4, 7.1 Hz, 2H), 1.81 (ddd, J=26.1, 14.0, 7.0 Hz, 2H), 1.33 (d, J=34.8 Hz, 9H); ¹⁹F NMR (376 MHz, DMSO-d₆) rotomers δ −70.35, −70.75; ESIMS m/z 295 ([M−H]⁻).

tert-Butyl (1-(ethylcarbamoyl)cyclopropyl)carbamate

The title molecule was isolated as a white solid (3.54 g, 68%): mp=113-116° C.; ¹H NMR (400 MHz, CDCl₃) δ 6.44 (bs, 1H), 5.09 (bs, 1H), 3.43-3.17 (m, 2H), 1.63-1.51 (m, 2H), 1.46 (s, 9H), 1.15 (t, J=7.3 Hz, 3H), 1.00-0.97 (m, 2H); (101 MHz, CDCl₃) δ 172.03, 155.89, 80.37, 35.53, 34.65, 28.23, 17.17, 14.85.

tert-Butyl (1-((2,2-difluoroethyl)carbamoyl)cyclopropyl)carbamate

The title molecule was isolated as a white solid (290 mg, 70%): mp=131-135° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 7.93 (bs, 1H), 7.39 (bs, 1H), 6.15-5.74 (m, 1H), 3.52-3.31 (m, 2H), 1.38 (s, 9H), 1.23-1.17 (m, 2H), 0.97-0.87 (m, 2H); ESIMS m/z 165.1 ([M-Boc]⁺).

tert-Butyl (1-((2-fluoroethyl)carbamoyl)cyclopropyl)carbamate

The title molecule was isolated as a white solid (250 mg, 62%): mp=121-125° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 7.80 (bs, 1H), 7.41 (bs, 1H), 4.47 (t, J=5.7 Hz, 1H), 4.34 (t, J=5.4 Hz, 1H), 3.43-3.31 (m, 2H), 1.38 (s, 9H), 1.22-1.18 (m, 2H), 0.87-0.84 (m, 2H); ESIMS m/z 146.2 ([M-Boc]⁺).

tert-Butyl (1-((3,3,3-trifluoropropyl)carbamoyl)cyclopropyl)carbamate

The title molecule was isolated as a white solid (550 mg, 58%): mp=146-148° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 7.80 (bs, 1H), 7.40 (bs, 1H), 3.34-3.27 (m, 2H), 2.43-2.32 (m, 2H), 1.38 (s, 9H), 1.22-1.18 (m, 2H), 0.87-0.83 (m, 2H); ESIMS m/z 197.1 ([M-Boc+H]⁺).

Example 131: Preparation of tert-Butyl 1-amino-N-(2,2,2-trifluoroethyl)cyclopropanecarboxamide hydrochloride

To tert-butyl (1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)carbamate (3.2 g, 11 mmol) in CH₂Cl₂ (20 mL) was added 4 M HCl in dioxane (20 mL). The solution was stirred for 18 h at ambient temperature. The reaction mixture was concentrated in vacuo and the residue placed in a 60° C. vacuum oven (24 h) to afforded the title compound as an off-white solid (2.3 g, 93%): ¹H NMR (400 MHz, DMSO-d₆) δ 8.77 (bs, 3H), 8.50 (t, J=6.3 Hz, 1H), 3.90 (qd, J=9.7, 6.1 Hz, 2H), 1.52-1.15 (m, 4H); ¹⁹F NMR (376 MHz, DMSO-d₆) δ −70.54; ¹³C NMR (101 MHz, DMSO-d₆) δ 175.33, 132.46 (q, J=280.8 Hz), 45.13 (q, J=34.34 Hz), 40.06, 17.57.

The following molecules was made in accordance with the procedure disclosed in Example 131:

1-(Ethylcarbamoyl)cyclopropanaminium chloride

The title molecule was isolated as a white solid (2.27 g, 98%): mp=165-196° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.69 (s, 3H), 7.89 (t, J=5.4 Hz, 1H), 3.10 (dd, J=7.4, 5.6 Hz, 2H), 1.43-1.32 (m, 2H), 1.31-1.23 (m, 2H), 1.01 (t, J=7.2 Hz, 3H); (101 MHz, DMSO-d₆) δ 168.41, 34.71, 33.93, 14.47, 11.89; IR (thin film) 3313, 2983, 1678, 1537, 1251, 1159 cm⁻¹.

1-((2,2-Difluoroethyl)carbamoyl)cyclopropanaminium chloride

The title molecule was isolated as a white solid (200 mg, 99%): mp=221-225° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 8.40 (bs, 3H), 8.12 (bs, 1H), 6.20-5.81 (m, 1H), 3.55-3.45 (m, 2H), 1.44-1.36 (m, 2H), 1.31-1.23 (m, 2H); ESIMS m/z 165.1 ([M+H]⁺).

1-((2-Fluoroethyl)carbamoyl)cyclopropanaminium chloride

The title molecule was isolated as a white solid (180 mg, 89%): mp=157-161° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 8.62 (bs, 3H), 8.00 (bs, 1H), 4.51 (t, J=5.1 Hz, 1H), 4.35 (t, J=4.5 Hz, 1H), 3.35-3.32 (m, 2H), 1.41-1.37 (m, 2H), 1.29-1.25 (m, 2H); ESIMS m/z 147.1 ([M+H]⁺).

1-((3,3,3-Trifluoropropyl)carbamoyl)cyclopropanaminium chloride

The title molecule was isolated as a white solid (250 mg, 80%): mp=156-158° C.; ¹H NMR (300 MHz, DMSO-d₆) δ 8.58 (bs, 3H), 7.99 (bs, 1H), 3.36-3.29 (m, 2H), 2.51-2.38 (m, 2H), 1.39-1.35 (m, 2H), 1.31-1.26 (m, 2H); ESIMS m/z 197.2 ([M+H]⁺).

Example 132: Preparation of 1-((2,2,2-Trifluoroethyl)carbamoyl)cyclobutanaminium 2,2,2-trifluoroacetate

To a stirred solution of tert-butyl 1-(2,2,2-trifluoroethylcarbamoyl)cyclobutylcarbamate (500 mg, 1.68 mmol) in CH₂Cl₂ (10 mL) was added trifluoroacetic acid (TFA, 1.0 mL) dropwise and the reaction mixture was stirred overnight. The volatiles were evaporated and the residue was triturated with pentane to give the title compound as colorless gum which was taken on to the next step without further purification (400 mg, 77%): ¹H NMR (300 MHz, DMSO-d₆) δ 9.14 (t, J=6.0 Hz, 1H), 8.52 (bs, 2H), 4.08-3.96 (m, 2H), 2.63-2.55 (m, 2H), 2.27-2.14 (m, 2H), 2.08-2.00 (m, 2H); ESIMS m/z 196.9 ([M+H]⁺); IR (thin film) 3364, 2949, 1680, 1033 cm⁻¹.

Example 133: Preparation of (E)-4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-N-(1-(2,2,2-trifluoroethylcarbamothioyl)cyclopropyl)-2-(trifluoromethyl)benzamide (F6)

To a stirred solution of (E)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-N-(1-(2,2,2-trifluoroethylcarbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide (200 mg, 0.31 mmol) in CH₂Cl₂ (20 mL) was added P₄S₁₀ (34 mg, 0.155 mmol) and hexamethyldisiloxane (HMDO, 0.1 mL, 0.517 mmol) and the reaction mixture was refluxed for 4 h. The reaction mixture was cooled to room temperature and another portion of P₄S₁₀ (34 mg, 0.155 mmol) and HMDO (0.1 mL, 0.517 mmol) were added and the reaction mixture was refluxed for 16 h. The reaction mixture was concentrated under reduced pressure and the residue was purified by flash chromatography on silica (100-200 mesh) eluting with 10% EtOAc in hexane to give the title compounds as yellow gum (37 mg, 18%). Characterization data for this molecule is listed in Table 2.

Example 135: Isolation of (R,E)-4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide (F8A)

and (S,E)-4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N-(1-((2,2,2-trifluoroethyl)carbamoyl)cyclopropyl)-2-(trifluoromethyl)benzamide (F8B)

The enanteomeric pair of F8, prepared as in Example 28, were separated by chiral HPLC using Chiralpak® IA (4.6×250 mm) 5 μm column using 0.1% TFA in hexane and isopropanol as the mobile phase (isocratic 70:30) with a flow rate 1.0 mL/min at ambient temperature. Enantiomer F8A (isomer 1) was collected at a retention time of 10.62 min. Enantiomer F8B (isomer 2) was collected at 12.28 min. Characterization data for these molecules are listed in Table 2A.

Example 136: Preparation of 1-(3,5-Difluoro-4-methoxyphenyl)-2,2,2-trifluoroethanone

Isopropyl magnesium chloride lithium chloride complex (22.0 mL, 28.02 mmol) was added dropwise to a stirred solution of 5-bromo-1,3-difluoro-2-methoxybenzene (5.0 g, 22.42 mmol) at −5° C. in THF (100 mL) and the reaction mixture was stirred at same temperature for 30 min. Methyl trifluoroacetate (3.67 g, 28.69 mmol) was added dropwise and then the reaction mixture was stirred at ambient temperature for 2 h. A 2 N HCl solution (200 mL) was added to quench the reaction and then it was extracted with diethylether. The organic combined layers were washed with brine dried (Na₂SO₄), filtered and concentrated to afford the title compound (5.4 g, crude) as a yellow liquid. The material was taken on to next step without further purification. ¹H NMR (400 MHz, CDCl₃) δ 7.68-7.60 (m, 2H), 4.19 (s, 3H); ESIMS m/z 240.1 ([M]⁺).

The following molecule was prepared in accordance with the procedures disclosed in Example 136:

2,6-Difluoro-4-(2,2,2-trifluoroacetyl)benzonitrile

¹H NMR (400 MHz, CDCl3) δ 7.45 (d, J=8.4 Hz, 1H), 7.37 (d, J=8.4 Hz, 1H); EIMS m/z 235.1 ([M]⁺).

The following prophetic molecules could be made in accordance with the procedures disclosed in this application:

Compound Number Structure P1 

P2 

P3 

P4 

P5 

P6 

P7 

P8 

P9 

P10

P11

P12

P13

P14

P15

P16

P17

P18

P19

P20

P21

P22

P23

P24

P25

P26

P27

P28

P29

P30

P31

P32

P33

P34

P35

P36

P37

P38

P39

P40

P41

P42

P43

P44

P45

P46

P47

P48

P49

P50

P51

The following prophetic molecules could be made in accordance with the procedures disclosed in this application:

Compound Number R1 R2 R3 R4 R6 R8 R10 W2 R15 P52 F F F H CF₃ CF₃ H O CH₂CF₃ P53 F F F H CF₃ CF₃ Br O CH₂CF₃ P54 F F F H CF₃ CF₃ Cl O CH₂CF₃ P55 F F F H CF₃ CF₃ CF₃ O CH₂CF₃ P56 F F F H CF₃ CF₃ CH₃ O CH₂CF₃ P57 F F F H CF₂CF₃ H H O CH₂CF₃ P58 F F F H CF₂CF₃ H Br O CH₂CF₃ P59 F F F H CF₂CF₃ H Cl O CH₂CF₃ P60 F F F H CF₂CF₃ H CF₃ O CH₂CF₃ P61 F F F H CF₂CF₃ H CH₃ O CH₂CF₃ P62 F F F H CF₃ H H O CH₂CF₃ P63 F F F H CF₃ H Br O CH₂CF₃ P64 F F F H CF₃ H Cl O CH₂CF₃ P65 F F F H CF₃ H CF₃ O CH₂CF₃ P66 F F F H CF₃ H CH₃ O CH₂CF₃ P67 F F F H CF₃ H H S CH₂CF₃ P68 F F F H CF₃ H Br S CH₂CF₃ P69 F F F H CF₃ H Cl S CH₂CF₃ P70 F F F H CF₃ H CF₃ S CH₂CF₃ P71 F F F H CF₃ H CH₃ S CH₂CF₃ P72 F F F H CF₃ H H O CH₂CHF₂ P73 F F F H CF₃ H Br O CH₂CHF₂ P74 F F F H CF₃ H Cl O CH₂CHF₂ P75 F F F H CF₃ H CF₃ O CH₂CHF₂ P76 F F F H CF₃ H CH₃ O CH₂CHF₂ P77 F F F H CF₃ H H O CH₂CH₂F P78 F F F H CF₃ H Br O CH₂CH₂F P79 F F F H CF₃ H Cl O CH₂CH₂F P80 F F F H CF₃ H CF₃ O CH₂CH₂F P81 F F F H CF₃ H CH₃ O CH₂CH₂F P82 F F F H CF₃ H H O CH₂CH₃ P83 F F F H CF₃ H Br O CH₂CH₃ P84 F F F H CF₃ H Cl O CH₂CH₃ P85 F F F H CF₃ H CF₃ O CH₂CH₃ P86 F F F H CF₃ H CH₃ O CH₂CH₃ P87 F F F H CF₃ H H O CH(CH₃)CF₃ P88 F F F H CF₃ H Br O CH(CH₃)CF₃ P89 F F F H CF₃ H Cl O CH(CH₃)CF₃ P90 F F F H CF₃ H CF₃ O CH(CH₃)CF₃ P91 F F F H CF₃ H CH₃ O CH(CH₃)CF₃ P92 F F F H CF₃ H H O CH₂CH₂CF₃ P93 F F F H CF₃ H Br O CH₂CH₂CF₃ P94 F F F H CF₃ H Cl O CH₂CH₂CF₃ P95 F F F H CF₃ H CF₃ O CH₂CH₂CF₃ P96 F F F H CF₃ H CH₃ O CH₂CH₂CF₃ P97 Cl Cl H Cl CF₃ CF₃ H O CH₂CF₃ P98 Cl Cl H Cl CF₃ CF₃ Br O CH₂CF₃ P99 Cl Cl H Cl CF₃ CF₃ Cl O CH₂CF₃ P100 Cl Cl H Cl CF₃ CF₃ CF₃ O CH₂CF₃ P101 Cl Cl H Cl CF₃ CF₃ CH₃ O CH₂CF₃ P102 Cl Cl H Cl CF₂CF₃ H H O CH₂CF₃ P103 Cl Cl H Cl CF₂CF₃ H Br O CH₂CF₃ P104 Cl Cl H Cl CF₂CF₃ H Cl O CH₂CF₃ P105 Cl Cl H Cl CF₂CF₃ H CF₃ O CH₂CF₃ P106 Cl Cl H Cl CF₂CF₃ H CH₃ O CH₂CF₃ P107 Cl Cl H Cl CF₃ H H O CH₂CF₃ P108 Cl Cl H Cl CF₃ H Br O CH₂CF₃ P109 Cl Cl H Cl CF₃ H Cl O CH₂CF₃ P110 Cl Cl H Cl CF₃ H CF₃ O CH₂CF₃ P111 Cl Cl H Cl CF₃ H CH₃ O CH₂CF₃ P112 Cl Cl H Cl CF₃ H H S CH₂CF₃ P113 Cl Cl H Cl CF₃ H Br S CH₂CF₃ P114 Cl Cl H Cl CF₃ H Cl S CH₂CF₃ P115 Cl Cl H Cl CF₃ H CF₃ S CH₂CF₃ P116 Cl Cl H Cl CF₃ H CH₃ S CH₂CF₃ P117 Cl Cl H Cl CF₃ H H O CH₂CHF₂ P118 Cl Cl H Cl CF₃ H Br O CH₂CHF₂ P119 Cl Cl H Cl CF₃ H Cl O CH₂CHF₂ P120 Cl Cl H Cl CF₃ H CF₃ O CH₂CHF₂ P121 Cl Cl H Cl CF₃ H CH₃ O CH₂CHF₂ P122 Cl Cl H Cl CF₃ H H O CH₂CH₂F P123 Cl Cl H Cl CF₃ H Br O CH₂CH₂F P124 Cl Cl H Cl CF₃ H Cl O CH₂CH₂F P125 Cl Cl H Cl CF₃ H CF₃ O CH₂CH₂F P126 Cl Cl H Cl CF₃ H CH₃ O CH₂CH₂F P127 Cl Cl H Cl CF₃ H H O CH₂CH₃ P128 Cl Cl H Cl CF₃ H Br O CH₂CH₃ P129 Cl Cl H Cl CF₃ H Cl O CH₂CH₃ P130 Cl Cl H Cl CF₃ H CF₃ O CH₂CH₃ P131 Cl Cl H Cl CF₃ H CH₃ O CH₂CH₃ P132 Cl Cl H Cl CF₃ H H O CH(CH₃)CF₃ P133 Cl Cl H Cl CF₃ H Br O CH(CH₃)CF₃ P134 Cl Cl H Cl CF₃ H Cl O CH(CH₃)CF₃ P135 Cl Cl H Cl CF₃ H CF₃ O CH(CH₃)CF₃ P136 Cl Cl H Cl CF₃ H CH₃ O CH(CH₃)CF₃ P137 Cl Cl H Cl CF₃ H H O CH₂CH₂CF₃ P138 Cl Cl H Cl CF₃ H Br O CH₂CH₂CF₃ P139 Cl Cl H Cl CF₃ H Cl O CH₂CH₂CF₃ P140 Cl Cl H Cl CF₃ H CF₃ O CH₂CH₂CF₃ P141 Cl Cl H Cl CF₃ H CH₃ O CH₂CH₂CF₃ P142 H H H OCF₃ CF₃ CF₃ H O CH₂CF₃ P143 H H H OCF₃ CF₃ CF₃ Br O CH₂CF₃ P144 H H H OCF₃ CF₃ CF₃ Cl O CH₂CF₃ P145 H H H OCF₃ CF₃ CF₃ CF₃ O CH₂CF₃ P146 H H H OCF₃ CF₃ CF₃ CH₃ O CH₂CF₃ P147 H H H OCF₃ CF₂CF₃ H H O CH₂CF₃ P148 H H H OCF₃ CF₂CF₃ H Br O CH₂CF₃ P149 H H H OCF₃ CF₂CF₃ H Cl O CH₂CF₃ P150 H H H OCF₃ CF₂CF₃ H CF₃ O CH₂CF₃ P151 H H H OCF₃ CF₂CF₃ H CH₃ O CH₂CF₃ P152 H H H OCF₃ CF₃ H H O CH₂CF₃ P153 H H H OCF₃ CF₃ H Br O CH₂CF₃ P154 H H H OCF₃ CF₃ H Cl O CH₂CF₃ P155 H H H OCF₃ CF₃ H CF₃ O CH₂CF₃ P156 H H H OCF₃ CF₃ H CH₃ O CH₂CF₃ P157 H H H OCF₃ CF₃ H H S CH₂CF₃ P158 H H H OCF₃ CF₃ H Br S CH₂CF₃ P159 H H H OCF₃ CF₃ H Cl S CH₂CF₃ P160 H H H OCF₃ CF₃ H CF₃ S CH₂CF₃ P161 H H H OCF₃ CF₃ H CH₃ S CH₂CF₃ P162 H H H OCF₃ CF₃ H H O CH₂CHF₂ P163 H H H OCF₃ CF₃ H Br O CH₂CHF₂ P164 H H H OCF₃ CF₃ H Cl O CH₂CHF₂ P165 H H H OCF₃ CF₃ H CF₃ O CH₂CHF₂ P166 H H H OCF₃ CF₃ H CH₃ O CH₂CHF₂ P167 H H H OCF₃ CF₃ H H O CH₂CH₂F P168 H H H OCF₃ CF₃ H Br O CH₂CH₂F P169 H H H OCF₃ CF₃ H Cl O CH₂CH₂F P170 H H H OCF₃ CF₃ H CF₃ O CH₂CH₂F P171 H H H OCF₃ CF₃ H CH₃ O CH₂CH₂F P172 H H H OCF₃ CF₃ H H O CH₂CH₃ P173 H H H OCF₃ CF₃ H Br O CH₂CH₃ P174 H H H OCF₃ CF₃ H Cl O CH₂CH₃ P175 H H H OCF₃ CF₃ H CF₃ O CH₂CH₃ P176 H H H OCF₃ CF₃ H CH₃ O CH₂CH₃ P177 H H H OCF₃ CF₃ H H O CH(CH₃)CF₃ P178 H H H OCF₃ CF₃ H Br O CH(CH₃)CF₃ P179 H H H OCF₃ CF₃ H Cl O CH(CH₃)CF₃ P180 H H H OCF₃ CF₃ H CF₃ O CH(CH₃)CF₃ P181 H H H OCF₃ CF₃ H CH₃ O CH(CH₃)CF₃ P182 H H H OCF₃ CF₃ H H O CH₂CH₂CF₃ P183 H H H OCF₃ CF₃ H Br O CH₂CH₂CF₃ P184 H H H OCF₃ CF₃ H Cl O CH₂CH₂CF₃ P185 H H H OCF₃ CF₃ H CF₃ O CH₂CH₂CF₃ P186 H H H OCF₃ CF₃ H CH₃ O CH₂CH₂CF₃ P187 H F H Br CF₃ CF₃ H O CH₂CF₃ P188 H F H Br CF₃ CF₃ Br O CH₂CF₃ P189 H F H Br CF₃ CF₃ Cl O CH₂CF₃ P190 H F H Br CF₃ CF₃ CF₃ O CH₂CF₃ P191 H F H Br CF₃ CF₃ CH₃ O CH₂CF₃ P192 H F H Br CF₂CF₃ H H O CH₂CF₃ P193 H F H Br CF₂CF₃ H Br O CH₂CF₃ P194 H F H Br CF₂CF₃ H Cl O CH₂CF₃ P195 H F H Br CF₂CF₃ H CF₃ O CH₂CF₃ P196 H F H Br CF₂CF₃ H CH₃ O CH₂CF₃ P197 H F H Br CF₃ H H O CH₂CF₃ P198 H F H Br CF₃ H Br O CH₂CF₃ P199 H F H Br CF₃ H Cl O CH₂CF₃ P200 H F H Br CF₃ H CF₃ O CH₂CF₃ P201 H F H Br CF₃ H CH₃ O CH₂CF₃ P202 H F H Br CF₃ H H S CH₂CF₃ P203 H F H Br CF₃ H Br S CH₂CF₃ P204 H F H Br CF₃ H Cl S CH₂CF₃ P205 H F H Br CF₃ H CF₃ S CH₂CF₃ P206 H F H Br CF₃ H CH₃ S CH₂CF₃ P207 H F H Br CF₃ H H O CH₂CHF₂ P208 H F H Br CF₃ H Br O CH₂CHF₂ P209 H F H Br CF₃ H Cl O CH₂CHF₂ P210 H F H Br CF₃ H CF₃ O CH₂CHF₂ P211 H F H Br CF₃ H CH₃ O CH₂CHF₂ P212 H F H Br CF₃ H H O CH₂CH₂F P213 H F H Br CF₃ H Br O CH₂CH₂F P214 H F H Br CF₃ H Cl O CH₂CH₂F P215 H F H Br CF₃ H CF₃ O CH₂CH₂F P216 H F H Br CF₃ H CH₃ O CH₂CH₂F P217 H F H Br CF₃ H H O CH₂CH₃ P218 H F H Br CF₃ H Br O CH₂CH₃ P219 H F H Br CF₃ H Cl O CH₂CH₃ P220 H F H Br CF₃ H CF₃ O CH₂CH₃ P221 H F H Br CF₃ H CH₃ O CH₂CH₃ P222 H F H Br CF₃ H H O CH(CH₃)CF₃ P223 H F H Br CF₃ H Br O CH(CH₃)CF₃ P224 H F H Br CF₃ H Cl O CH(CH₃)CF₃ P225 H F H Br CF₃ H CF₃ O CH(CH₃)CF₃ P226 H F H Br CF₃ H CH₃ O CH(CH₃)CF₃ P227 H F H Br CF₃ H H O CH₂CH₂CF₃ P228 H F H Br CF₃ H Br O CH₂CH₂CF₃ P229 H F H Br CF₃ H Cl O CH₂CH₂CF₃ P230 H F H Br CF₃ H CF₃ O CH₂CH₂CF₃ P231 H F H Br CF₃ H CH₃ O CH₂CH₂CF₃ P232 H CH₃ Cl H CF₃ CF₃ H O CH₂CF₃ P233 H CH₃ Cl H CF₃ CF₃ Br O CH₂CF₃ P234 H CH₃ Cl H CF₃ CF₃ Cl O CH₂CF₃ P235 H CH₃ Cl H CF₃ CF₃ CF₃ O CH₂CF₃ P236 H CH₃ Cl H CF₃ CF₃ CH₃ O CH₂CF₃ P237 H CH₃ Cl H CF₂CF₃ H H O CH₂CF₃ P238 H CH₃ Cl H CF₂CF₃ H Br O CH₂CF₃ P239 H CH₃ Cl H CF₂CF₃ H Cl O CH₂CF₃ P240 H CH₃ Cl H CF₂CF₃ H CF₃ O CH₂CF₃ P241 H CH₃ Cl H CF₂CF₃ H CH₃ O CH₂CF₃ P242 H CH₃ Cl H CF₃ H H O CH₂CF₃ P243 H CH₃ Cl H CF₃ H Br O CH₂CF₃ P244 H CH₃ Cl H CF₃ H Cl O CH₂CF₃ P245 H CH₃ Cl H CF₃ H CF₃ O CH₂CF₃ P246 H CH₃ Cl H CF₃ H CH₃ O CH₂CF₃ P247 H CH₃ Cl H CF₃ H H S CH₂CF₃ P248 H CH₃ Cl H CF₃ H Br S CH₂CF₃ P249 H CH₃ Cl H CF₃ H Cl S CH₂CF₃ P250 H CH₃ Cl H CF₃ H CF₃ S CH₂CF₃ P251 H CH₃ Cl H CF₃ H CH₃ S CH₂CF₃ P252 H CH₃ Cl H CF₃ H H O CH₂CHF₂ P253 H CH₃ Cl H CF₃ H Br O CH₂CHF₂ P254 H CH₃ Cl H CF₃ H Cl O CH₂CHF₂ P255 H CH₃ Cl H CF₃ H CF₃ O CH₂CHF₂ P256 H CH₃ Cl H CF₃ H CH₃ O CH₂CHF₂ P257 H CH₃ Cl H CF₃ H H O CH₂CH₂F P258 H CH₃ Cl H CF₃ H Br O CH₂CH₂F P259 H CH₃ Cl H CF₃ H Cl O CH₂CH₂F P260 H CH₃ Cl H CF₃ H CF₃ O CH₂CH₂F P261 H CH₃ Cl H CF₃ H CH₃ O CH₂CH₂F P262 H CH₃ Cl H CF₃ H H O CH₂CH₃ P263 H CH₃ Cl H CF₃ H Br O CH₂CH₃ P264 H CH₃ Cl H CF₃ H Cl O CH₂CH₃ P265 H CH₃ Cl H CF₃ H CF₃ O CH₂CH₃ P266 H CH₃ Cl H CF₃ H CH₃ O CH₂CH₃ P267 H CH₃ Cl H CF₃ H H O CH(CH₃)CF₃ P268 H CH₃ Cl H CF₃ H Br O CH(CH₃)CF₃ P269 H CH₃ Cl H CF₃ H Cl O CH(CH₃)CF₃ P270 H CH₃ Cl H CF₃ H CF₃ O CH(CH₃)CF₃ P271 H CH₃ Cl H CF₃ H CH₃ O CH(CH₃)CF₃ P272 H CH₃ Cl H CF₃ H H O CH₂CH₂CF₃ P273 H CH₃ Cl H CF₃ H Br O CH₂CH₂CF₃ P274 H CH₃ Cl H CF₃ H Cl O CH₂CH₂CF₃ P275 H CH₃ Cl H CF₃ H CF₃ O CH₂CH₂CF₃ P276 H CH₃ Cl H CF₃ H CH₃ O CH₂CH₂CF₃ P277 H Cl CH₃ H CF₃ CF₃ H O CH₂CF₃ P278 H Cl CH₃ H CF₃ CF₃ Br O CH₂CF₃ P279 H Cl CH₃ H CF₃ CF₃ Cl O CH₂CF₃ P280 H Cl CH₃ H CF₃ CF₃ CF₃ O CH₂CF₃ P281 H Cl CH₃ H CF₃ CF₃ CH₃ O CH₂CF₃ P282 H Cl CH₃ H CF₂CF₃ H H O CH₂CF₃ P283 H Cl CH₃ H CF₂CF₃ H Br O CH₂CF₃ P284 H Cl CH₃ H CF₂CF₃ H Cl O CH₂CF₃ P285 H Cl CH₃ H CF₂CF₃ H CF₃ O CH₂CF₃ P286 H Cl CH₃ H CF₂CF₃ H CH₃ O CH₂CF₃ P287 H Cl CH₃ H CF₃ H H O CH₂CF₃ P288 H Cl CH₃ H CF₃ H Br O CH₂CF₃ P289 H Cl CH₃ H CF₃ H Cl O CH₂CF₃ P290 H Cl CH₃ H CF₃ H CF₃ O CH₂CF₃ P291 H Cl CH₃ H CF₃ H CH₃ O CH₂CF₃ P292 H Cl CH₃ H CF₃ H H S CH₂CF₃ P293 H Cl CH₃ H CF₃ H Br S CH₂CF₃ P294 H Cl CH₃ H CF₃ H Cl S CH₂CF₃ P295 H Cl CH₃ H CF₃ H CF₃ S CH₂CF₃ P296 H Cl CH₃ H CF₃ H CH₃ S CH₂CF₃ P297 H Cl CH₃ H CF₃ H H O CH₂CHF₂ P298 H Cl CH₃ H CF₃ H Br O CH₂CHF₂ P299 H Cl CH₃ H CF₃ H Cl O CH₂CHF₂ P300 H Cl CH₃ H CF₃ H CF₃ O CH₂CHF₂ P301 H Cl CH₃ H CF₃ H CH₃ O CH₂CHF₂ P302 H Cl CH₃ H CF₃ H H O CH₂CH₂F P303 H Cl CH₃ H CF₃ H Br O CH₂CH₂F P304 H Cl CH₃ H CF₃ H Cl O CH₂CH₂F P305 H Cl CH₃ H CF₃ H CF₃ O CH₂CH₂F P306 H Cl CH₃ H CF₃ H CH₃ O CH₂CH₂F P307 H Cl CH₃ H CF₃ H H O CH₂CH₃ P308 H Cl CH₃ H CF₃ H Br O CH₂CH₃ P309 H Cl CH₃ H CF₃ H Cl O CH₂CH₃ P310 H Cl CH₃ H CF₃ H CF₃ O CH₂CH₃ P311 H Cl CH₃ H CF₃ H CH₃ O CH₂CH₃ P312 H Cl CH₃ H CF₃ H H O CH(CH₃)CF₃ P313 H Cl CH₃ H CF₃ H Br O CH(CH₃)CF₃ P314 H Cl CH₃ H CF₃ H Cl O CH(CH₃)CF₃ P315 H Cl CH₃ H CF₃ H CF₃ O CH(CH₃)CF₃ P316 H Cl CH₃ H CF₃ H CH₃ O CH(CH₃)CF₃ P317 H Cl CH₃ H CF₃ H H O CH₂CH₂CF₃ P318 H Cl CH₃ H CF₃ H Br O CH₂CH₂CF₃ P319 H Cl CH₃ H CF₃ H Cl O CH₂CH₂CF₃ P320 H Cl CH₃ H CF₃ H CF₃ O CH₂CH₂CF₃ P321 H Cl CH₃ H CF₃ H CH₃ O CH₂CH₂CF₃ P322 H CH₃ F CH₃ CF₃ CF₃ H O CH₂CF₃ P323 H CH₃ F CH₃ CF₃ CF₃ Br O CH₂CF₃ P324 H CH₃ F CH₃ CF₃ CF₃ Cl O CH₂CF₃ P325 H CH₃ F CH₃ CF₃ CF₃ CF₃ O CH₂CF₃ P326 H CH₃ F CH₃ CF₃ CF₃ CH₃ O CH₂CF₃ P327 H CH₃ F CH₃ CF₂CF₃ H H O CH₂CF₃ P328 H CH₃ F CH₃ CF₂CF₃ H Br O CH₂CF₃ P329 H CH₃ F CH₃ CF₂CF₃ H Cl O CH₂CF₃ P330 H CH₃ F CH₃ CF₂CF₃ H CF₃ O CH₂CF₃ P331 H CH₃ F CH₃ CF₂CF₃ H CH₃ O CH₂CF₃ P332 H CH₃ F CH₃ CF₃ H H O CH₂CF₃ P333 H CH₃ F CH₃ CF₃ H Br O CH₂CF₃ P334 H CH₃ F CH₃ CF₃ H Cl O CH₂CF₃ P335 H CH₃ F CH₃ CF₃ H CF₃ O CH₂CF₃ P336 H CH₃ F CH₃ CF₃ H CH₃ O CH₂CF₃ P337 H CH₃ F CH₃ CF₃ H H S CH₂CF₃ P338 H CH₃ F CH₃ CF₃ H Br S CH₂CF₃ P339 H CH₃ F CH₃ CF₃ H Cl S CH₂CF₃ P340 H CH₃ F CH₃ CF₃ H CF₃ S CH₂CF₃ P341 H CH₃ F CH₃ CF₃ H CH₃ S CH₂CF₃ P342 H CH₃ F CH₃ CF₃ H H O CH₂CHF₂ P343 H CH₃ F CH₃ CF₃ H Br O CH₂CHF₂ P344 H CH₃ F CH₃ CF₃ H Cl O CH₂CHF₂ P345 H CH₃ F CH₃ CF₃ H CF₃ O CH₂CHF₂ P346 H CH₃ F CH₃ CF₃ H CH₃ O CH₂CHF₂ P347 H CH₃ F CH₃ CF₃ H H O CH₂CH₂F P348 H CH₃ F CH₃ CF₃ H Br O CH₂CH₂F P349 H CH₃ F CH₃ CF₃ H Cl O CH₂CH₂F P350 H CH₃ F CH₃ CF₃ H CF₃ O CH₂CH₂F P351 H CH₃ F CH₃ CF₃ H CH₃ O CH₂CH₂F P352 H CH₃ F CH₃ CF₃ H H O CH₂CH₃ P353 H CH₃ F CH₃ CF₃ H Br O CH₂CH₃ P354 H CH₃ F CH₃ CF₃ H Cl O CH₂CH₃ P355 H CH₃ F CH₃ CF₃ H CF₃ O CH₂CH₃ P356 H CH₃ F CH₃ CF₃ H CH₃ O CH₂CH₃ P357 H CH₃ F CH₃ CF₃ H H O CH(CH₃)CF₃ P358 H CH₃ F CH₃ CF₃ H Br O CH(CH₃)CF₃ P359 H CH₃ F CH₃ CF₃ H Cl O CH(CH₃)CF₃ P360 H CH₃ F CH₃ CF₃ H CF₃ O CH(CH₃)CF₃ P361 H CH₃ F CH₃ CF₃ H CH₃ O CH(CH₃)CF₃ P362 H CH₃ F CH₃ CF₃ H H O CH₂CH₂CF₃ P363 H CH₃ F CH₃ CF₃ H Br O CH₂CH₂CF₃ P364 H CH₃ F CH₃ CF₃ H Cl O CH₂CH₂CF₃ P365 H CH₃ F CH₃ CF₃ H CF₃ O CH₂CH₂CF₃ P366 H CH₃ F CH₃ CF₃ H CH₃ O CH₂CH₂CF₃ P367 H Cl H Br CF₃ CF₃ H O CH₂CF₃ P368 H Cl H Br CF₃ CF₃ Br O CH₂CF₃ P369 H Cl H Br CF₃ CF₃ Cl O CH₂CF₃ P370 H Cl H Br CF₃ CF₃ CF₃ O CH₂CF₃ P371 H Cl H Br CF₃ CF₃ CH₃ O CH₂CF₃ P372 H Cl H Br CF₂CF₃ H H O CH₂CF₃ P373 H Cl H Br CF₂CF₃ H Br O CH₂CF₃ P374 H Cl H Br CF₂CF₃ H Cl O CH₂CF₃ P375 H Cl H Br CF₂CF₃ H CF₃ O CH₂CF₃ P376 H Cl H Br CF₂CF₃ H CH₃ O CH₂CF₃ P377 H Cl H Br CF₃ H H O CH₂CF₃ P378 H Cl H Br CF₃ H Br O CH₂CF₃ P379 H Cl H Br CF₃ H Cl O CH₂CF₃ P380 H Cl H Br CF₃ H CF₃ O CH₂CF₃ P381 H Cl H Br CF₃ H CH₃ O CH₂CF₃ P382 H Cl H Br CF₃ H H S CH₂CF₃ P383 H Cl H Br CF₃ H Br S CH₂CF₃ P384 H Cl H Br CF₃ H Cl S CH₂CF₃ P385 H Cl H Br CF₃ H CF₃ S CH₂CF₃ P386 H Cl H Br CF₃ H CH₃ S CH₂CF₃ P387 H Cl H Br CF₃ H H O CH₂CHF₂ P388 H Cl H Br CF₃ H Br O CH₂CHF₂ P389 H Cl H Br CF₃ H Cl O CH₂CHF₂ P390 H Cl H Br CF₃ H CF₃ O CH₂CHF₂ P391 H Cl H Br CF₃ H CH₃ O CH₂CHF₂ P392 H Cl H Br CF₃ H H O CH₂CH₂F P393 H Cl H Br CF₃ H Br O CH₂CH₂F P394 H Cl H Br CF₃ H Cl O CH₂CH₂F P395 H Cl H Br CF₃ H CF₃ O CH₂CH₂F P396 H Cl H Br CF₃ H CH₃ O CH₂CH₂F P397 H Cl H Br CF₃ H H O CH₂CH₃ P398 H Cl H Br CF₃ H Br O CH₂CH₃ P399 H Cl H Br CF₃ H Cl O CH₂CH₃ P400 H Cl H Br CF₃ H CF₃ O CH₂CH₃ P401 H Cl H Br CF₃ H CH₃ O CH₂CH₃ P402 H Cl H Br CF₃ H H O CH(CH₃)CF₃ P403 H Cl H Br CF₃ H Br O CH(CH₃)CF₃ P404 H Cl H Br CF₃ H Cl O CH(CH₃)CF₃ P405 H Cl H Br CF₃ H CF₃ O CH(CH₃)CF₃ P406 H Cl H Br CF₃ H CH₃ O CH(CH₃)CF₃ P407 H Cl H Br CF₃ H H O CH₂CH₂CF₃ P408 H Cl H Br CF₃ H Br O CH₂CH₂CF₃ P409 H Cl H Br CF₃ H Cl O CH₂CH₂CF₃ P410 H Cl H Br CF₃ H CF₃ O CH₂CH₂CF₃ P411 H Cl H Br CF₃ H CH₃ O CH₂CH₂CF₃ P412 H H Br Br CF₃ CF₃ H O CH₂CF₃ P413 H H Br Br CF₃ CF₃ Br O CH₂CF₃ P414 H H Br Br CF₃ CF₃ Cl O CH₂CF₃ P415 H H Br Br CF₃ CF₃ CF₃ O CH₂CF₃ P416 H H Br Br CF₃ CF₃ CH₃ O CH₂CF₃ P417 H H Br Br CF₂CF₃ H H O CH₂CF₃ P418 H H Br Br CF₂CF₃ H Br O CH₂CF₃ P419 H H Br Br CF₂CF₃ H Cl O CH₂CF₃ P420 H H Br Br CF₂CF₃ H CF₃ O CH₂CF₃ P421 H H Br Br CF₂CF₃ H CH₃ O CH₂CF₃ P422 H H Br Br CF₃ H H O CH₂CF₃ P423 H H Br Br CF₃ H Br O CH₂CF₃ P424 H H Br Br CF₃ H Cl O CH₂CF₃ P425 H H Br Br CF₃ H CF₃ O CH₂CF₃ P426 H H Br Br CF₃ H CH₃ O CH₂CF₃ P427 H H Br Br CF₃ H H S CH₂CF₃ P428 H H Br Br CF₃ H Br S CH₂CF₃ P429 H H Br Br CF₃ H Cl S CH₂CF₃ P430 H H Br Br CF₃ H CF₃ S CH₂CF₃ P431 H H Br Br CF₃ H CH₃ S CH₂CF₃ P432 H H Br Br CF₃ H H O CH₂CHF₂ P433 H H Br Br CF₃ H Br O CH₂CHF₂ P434 H H Br Br CF₃ H Cl O CH₂CHF₂ P435 H H Br Br CF₃ H CF₃ O CH₂CHF₂ P436 H H Br Br CF₃ H CH₃ O CH₂CHF₂ P437 H H Br Br CF₃ H H O CH₂CH₂F P438 H H Br Br CF₃ H Br O CH₂CH₂F P439 H H Br Br CF₃ H Cl O CH₂CH₂F P440 H H Br Br CF₃ H CF₃ O CH₂CH₂F P441 H H Br Br CF₃ H CH₃ O CH₂CH₂F P442 H H Br Br CF₃ H H O CH₂CH₃ P443 H H Br Br CF₃ H Br O CH₂CH₃ P444 H H Br Br CF₃ H Cl O CH₂CH₃ P445 H H Br Br CF₃ H CF₃ O CH₂CH₃ P446 H H Br Br CF₃ H CH₃ O CH₂CH₃ P447 H H Br Br CF₃ H H O CH(CH₃)CF₃ P448 H H Br Br CF₃ H Br O CH(CH₃)CF₃ P449 H H Br Br CF₃ H Cl O CH(CH₃)CF₃ P450 H H Br Br CF₃ H CF₃ O CH(CH₃)CF₃ P451 H H Br Br CF₃ H CH₃ O CH(CH₃)CF₃ P452 H H Br Br CF₃ H H O CH₂CH₂CF₃ P453 H H Br Br CF₃ H Br O CH₂CH₂CF₃ P454 H H Br Br CF₃ H Cl O CH₂CH₂CF₃ P455 H H Br Br CF₃ H CF₃ O CH₂CH₂CF₃ P456 H H Br Br CF₃ H CH₃ O CH₂CH₂CF₃ P457 H H Cl NO₂ CF₃ CF₃ H O CH₂CF₃ P458 H H Cl NO₂ CF₃ CF₃ Br O CH₂CF₃ P459 H H Cl NO₂ CF₃ CF₃ Cl O CH₂CF₃ P460 H H Cl NO₂ CF₃ CF₃ CF₃ O CH₂CF₃ P461 H H Cl NO₂ CF₃ CF₃ CH₃ O CH₂CF₃ P462 H H Cl NO₂ CF₂CF₃ H H O CH₂CF₃ P463 H H Cl NO₂ CF₂CF₃ H Br O CH₂CF₃ P464 H H Cl NO₂ CF₂CF₃ H Cl O CH₂CF₃ P465 H H Cl NO₂ CF₂CF₃ H CF₃ O CH₂CF₃ P466 H H Cl NO₂ CF₂CF₃ H CH₃ O CH₂CF₃ P467 H H Cl NO₂ CF₃ H H O CH₂CF₃ P468 H H Cl NO₂ CF₃ H Br O CH₂CF₃ P469 H H Cl NO₂ CF₃ H Cl O CH₂CF₃ P470 H H Cl NO₂ CF₃ H CF₃ O CH₂CF₃ P471 H H Cl NO₂ CF₃ H CH₃ O CH₂CF₃ P472 H H Cl NO₂ CF₃ H H S CH₂CF₃ P473 H H Cl NO₂ CF₃ H Br S CH₂CF₃ P474 H H Cl NO₂ CF₃ H Cl S CH₂CF₃ P475 H H Cl NO₂ CF₃ H CF₃ S CH₂CF₃ P476 H H Cl NO₂ CF₃ H CH₃ S CH₂CF₃ P477 H H Cl NO₂ CF₃ H H O CH₂CHF₂ P478 H H Cl NO₂ CF₃ H Br O CH₂CHF₂ P479 H H Cl NO₂ CF₃ H Cl O CH₂CHF₂ P480 H H Cl NO₂ CF₃ H CF₃ O CH₂CHF₂ P481 H H Cl NO₂ CF₃ H CH₃ O CH₂CHF₂ P482 H H Cl NO₂ CF₃ H H O CH₂CH₂F P483 H H Cl NO₂ CF₃ H Br O CH₂CH₂F P484 H H Cl NO₂ CF₃ H Cl O CH₂CH₂F P485 H H Cl NO₂ CF₃ H CF₃ O CH₂CH₂F P486 H H Cl NO₂ CF₃ H CH₃ O CH₂CH₂F P487 H H Cl NO₂ CF₃ H H O CH₂CH₃ P488 H H Cl NO₂ CF₃ H Br O CH₂CH₃ P489 H H Cl NO₂ CF₃ H Cl O CH₂CH₃ P490 H H Cl NO₂ CF₃ H CF₃ O CH₂CH₃ P491 H H Cl NO₂ CF₃ H CH₃ O CH₂CH₃ P492 H H Cl NO₂ CF₃ H H O CH(CH₃)CF₃ P493 H H Cl NO₂ CF₃ H Br O CH(CH₃)CF₃ P494 H H Cl NO₂ CF₃ H Cl O CH(CH₃)CF₃ P495 H H Cl NO₂ CF₃ H CF₃ O CH(CH₃)CF₃ P496 H H Cl NO₂ CF₃ H CH₃ O CH(CH₃)CF₃ P497 H H Cl NO₂ CF₃ H H O CH₂CH₂CF₃ P498 H H Cl NO₂ CF₃ H Br O CH₂CH₂CF₃ P499 H H Cl NO₂ CF₃ H Cl O CH₂CH₂CF₃ P500 H H Cl NO₂ CF₃ H CF₃ O CH₂CH₂CF₃ P501 H H Cl NO₂ CF₃ H CH₃ O CH₂CH₂CF₃ P502 H H F CN CF₃ CF₃ H O CH₂CF₃ P503 H H F CN CF₃ CF₃ Br O CH₂CF₃ P504 H H F CN CF₃ CF₃ Cl O CH₂CF₃ P505 H H F CN CF₃ CF₃ CF₃ O CH₂CF₃ P506 H H F CN CF₃ CF₃ CH₃ O CH₂CF₃ P507 H H F CN CF₂CF₃ H H O CH₂CF₃ P508 H H F CN CF₂CF₃ H Br O CH₂CF₃ P509 H H F CN CF₂CF₃ H Cl O CH₂CF₃ P510 H H F CN CF₂CF₃ H CF₃ O CH₂CF₃ P511 H H F CN CF₂CF₃ H CH₃ O CH₂CF₃ P512 H H F CN CF₃ H H O CH₂CF₃ P513 H H F CN CF₃ H Br O CH₂CF₃ P514 H H F CN CF₃ H Cl O CH₂CF₃ P515 H H F CN CF₃ H CF₃ O CH₂CF₃ P516 H H F CN CF₃ H CH₃ O CH₂CF₃ P517 H H F CN CF₃ H H S CH₂CF₃ P518 H H F CN CF₃ H Br S CH₂CF₃ P519 H H F CN CF₃ H Cl S CH₂CF₃ P520 H H F CN CF₃ H CF₃ S CH₂CF₃ P521 H H F CN CF₃ H CH₃ S CH₂CF₃ P522 H H F CN CF₃ H H O CH₂CHF₂ P523 H H F CN CF₃ H Br O CH₂CHF₂ P524 H H F CN CF₃ H Cl O CH₂CHF₂ P525 H H F CN CF₃ H CF₃ O CH₂CHF₂ P526 H H F CN CF₃ H CH₃ O CH₂CHF₂ P527 H H F CN CF₃ H H O CH₂CH₂F P528 H H F CN CF₃ H Br O CH₂CH₂F P529 H H F CN CF₃ H Cl O CH₂CH₂F P530 H H F CN CF₃ H CF₃ O CH₂CH₂F P531 H H F CN CF₃ H CH₃ O CH₂CH₂F P532 H H F CN CF₃ H H O CH₂CH₃ P533 H H F CN CF₃ H Br O CH₂CH₃ P534 H H F CN CF₃ H Cl O CH₂CH₃ P535 H H F CN CF₃ H CF₃ O CH₂CH₃ P536 H H F CN CF₃ H CH₃ O CH₂CH₃ P537 H H F CN CF₃ H H O CH(CH₃)CF₃ P538 H H F CN CF₃ H Br O CH(CH₃)CF₃ P539 H H F CN CF₃ H Cl O CH(CH₃)CF₃ P540 H H F CN CF₃ H CF₃ O CH(CH₃)CF₃ P541 H H F CN CF₃ H CH₃ O CH(CH₃)CF₃ P542 H H F CN CF₃ H H O CH₂CH₂CF₃ P543 H H F CN CF₃ H Br O CH₂CH₂CF₃ P544 H H F CN CF₃ H Cl O CH₂CH₂CF₃ P545 H H F CN CF₃ H CF₃ O CH₂CH₂CF₃ P546 H H F CN CF₃ H CH₃ O CH₂CH₂CF₃ P547 H Cl OCF₃ Cl CF₃ CF₃ H O CH₂CF₃ P548 H Cl OCF₃ Cl CF₃ CF₃ Br O CH₂CF₃ P549 H Cl OCF₃ Cl CF₃ CF₃ Cl O CH₂CF₃ P550 H Cl OCF₃ Cl CF₃ CF₃ CF₃ O CH₂CF₃ P551 H Cl OCF₃ Cl CF₃ CF₃ CH₃ O CH₂CF₃ P552 H Cl OCF₃ Cl CF₂CF₃ H H O CH₂CF₃ P553 H Cl OCF₃ Cl CF₂CF₃ H Br O CH₂CF₃ P554 H Cl OCF₃ Cl CF₂CF₃ H Cl O CH₂CF₃ P555 H Cl OCF₃ Cl CF₂CF₃ H CF₃ O CH₂CF₃ P556 H Cl OCF₃ Cl CF₂CF₃ H CH₃ O CH₂CF₃ P557 H Cl OCF₃ Cl CF₃ H H O CH₂CF₃ P558 H Cl OCF₃ Cl CF₃ H Br O CH₂CF₃ P559 H Cl OCF₃ Cl CF₃ H Cl O CH₂CF₃ P560 H Cl OCF₃ Cl CF₃ H CF₃ O CH₂CF₃ P561 H Cl OCF₃ Cl CF₃ H CH₃ O CH₂CF₃ P562 H Cl OCF₃ Cl CF₃ H H S CH₂CF₃ P563 H Cl OCF₃ Cl CF₃ H Br S CH₂CF₃ P564 H Cl OCF₃ Cl CF₃ H Cl S CH₂CF₃ P565 H Cl OCF₃ Cl CF₃ H CF₃ S CH₂CF₃ P566 H Cl OCF₃ Cl CF₃ H CH₃ S CH₂CF₃ P567 H Cl OCF₃ Cl CF₃ H H O CH₂CHF₂ P568 H Cl OCF₃ Cl CF₃ H Br O CH₂CHF₂ P569 H Cl OCF₃ Cl CF₃ H Cl O CH₂CHF₂ P570 H Cl OCF₃ Cl CF₃ H CF₃ O CH₂CHF₂ P571 H Cl OCF₃ Cl CF₃ H CH₃ O CH₂CHF₂ P572 H Cl OCF₃ Cl CF₃ H H O CH₂CH₂F P573 H Cl OCF₃ Cl CF₃ H Br O CH₂CH₂F P574 H Cl OCF₃ Cl CF₃ H Cl O CH₂CH₂F P575 H Cl OCF₃ Cl CF₃ H CF₃ O CH₂CH₂F P576 H Cl OCF₃ Cl CF₃ H CH₃ O CH₂CH₂F P577 H Cl OCF₃ Cl CF₃ H H O CH₂CH₃ P578 H Cl OCF₃ Cl CF₃ H Br O CH₂CH₃ P579 H Cl OCF₃ Cl CF₃ H Cl O CH₂CH₃ P580 H Cl OCF₃ Cl CF₃ H CF₃ O CH₂CH₃ P581 H Cl OCF₃ Cl CF₃ H CH₃ O CH₂CH₃ P582 H Cl OCF₃ Cl CF₃ H H O CH(CH₃)CF₃ P583 H Cl OCF₃ Cl CF₃ H Br O CH(CH₃)CF₃ P584 H Cl OCF₃ Cl CF₃ H Cl O CH(CH₃)CF₃ P585 H Cl OCF₃ Cl CF₃ H CF₃ O CH(CH₃)CF₃ P586 H Cl OCF₃ Cl CF₃ H CH₃ O CH(CH₃)CF₃ P587 H Cl OCF₃ Cl CF₃ H H O CH₂CH₂CF₃ P588 H Cl OCF₃ Cl CF₃ H Br O CH₂CH₂CF₃ P589 H Cl OCF₃ Cl CF₃ H Cl O CH₂CH₂CF₃ P590 H Cl OCF₃ Cl CF₃ H CF₃ O CH₂CH₂CF₃ P591 H Cl OCF₃ Cl CF₃ H CH₃ O CH₂CH₂CF₃ P592 H Cl CN Cl CF₃ CF₃ H O CH₂CF₃ P593 H Cl CN Cl CF₃ CF₃ Br O CH₂CF₃ P594 H Cl CN Cl CF₃ CF₃ Cl O CH₂CF₃ P595 H Cl CN Cl CF₃ CF₃ CF₃ O CH₂CF₃ P596 H Cl CN Cl CF₃ CF₃ CH₃ O CH₂CF₃ P597 H Cl CN Cl CF₂CF₃ H H O CH₂CF₃ P598 H Cl CN Cl CF₂CF₃ H Br O CH₂CF₃ P599 H Cl CN Cl CF₂CF₃ H Cl O CH₂CF₃ P600 H Cl CN Cl CF₂CF₃ H CF₃ O CH₂CF₃ P601 H Cl CN Cl CF₂CF₃ H CH₃ O CH₂CF₃ P602 H Cl CN Cl CF₃ H H O CH₂CF₃ P603 H Cl CN Cl CF₃ H Br O CH₂CF₃ P604 H Cl CN Cl CF₃ H Cl O CH₂CF₃ P605 H Cl CN Cl CF₃ H CF₃ O CH₂CF₃ P606 H Cl CN Cl CF₃ H CH₃ O CH₂CF₃ P607 H Cl CN Cl CF₃ H H S CH₂CF₃ P608 H Cl CN Cl CF₃ H Br S CH₂CF₃ P609 H Cl CN Cl CF₃ H Cl S CH₂CF₃ P610 H Cl CN Cl CF₃ H CF₃ S CH₂CF₃ P611 H Cl CN Cl CF₃ H CH₃ S CH₂CF₃ P612 H Cl CN Cl CF₃ H H O CH₂CHF₂ P613 H Cl CN Cl CF₃ H Br O CH₂CHF₂ P614 H Cl CN Cl CF₃ H Cl O CH₂CHF₂ P615 H Cl CN Cl CF₃ H CF₃ O CH₂CHF₂ P616 H Cl CN Cl CF₃ H CH₃ O CH₂CHF₂ P617 H Cl CN Cl CF₃ H H O CH₂CH₂F P618 H Cl CN Cl CF₃ H Br O CH₂CH₂F P619 H Cl CN Cl CF₃ H Cl O CH₂CH₂F P620 H Cl CN Cl CF₃ H CF₃ O CH₂CH₂F P621 H Cl CN Cl CF₃ H CH₃ O CH₂CH₂F P622 H Cl CN Cl CF₃ H H O CH₂CH₃ P623 H Cl CN Cl CF₃ H Br O CH₂CH₃ P624 H Cl CN Cl CF₃ H Cl O CH₂CH₃ P625 H Cl CN Cl CF₃ H CF₃ O CH₂CH₃ P626 H Cl CN Cl CF₃ H CH₃ O CH₂CH₃ P627 H Cl CN Cl CF₃ H H O CH(CH₃)CF₃ P628 H Cl CN Cl CF₃ H Br O CH(CH₃)CF₃ P629 H Cl CN Cl CF₃ H Cl O CH(CH₃)CF₃ P630 H Cl CN Cl CF₃ H CF₃ O CH(CH₃)CF₃ P631 H Cl CN Cl CF₃ H CH₃ O CH(CH₃)CF₃ P632 H Cl CN Cl CF₃ H H O CH₂CH₂CF₃ P633 H Cl CN Cl CF₃ H Br O CH₂CH₂CF₃ P634 H Cl CN Cl CF₃ H Cl O CH₂CH₂CF₃ P635 H Cl CN Cl CF₃ H CF₃ O CH₂CH₂CF₃ P636 H Cl CN Cl CF₃ H CH₃ O CH₂CH₂CF₃ P637 H CH₃ H Br CF₃ CF₃ H O CH₂CF₃ P638 H CH₃ H Br CF₃ CF₃ Br O CH₂CF₃ P639 H CH₃ H Br CF₃ CF₃ Cl O CH₂CF₃ P640 H CH₃ H Br CF₃ CF₃ CF₃ O CH₂CF₃ P641 H CH₃ H Br CF₃ CF₃ CH₃ O CH₂CF₃ P642 H CH₃ H Br CF₂CF₃ H H O CH₂CF₃ P643 H CH₃ H Br CF₂CF₃ H Br O CH₂CF₃ P644 H CH₃ H Br CF₂CF₃ H Cl O CH₂CF₃ P645 H CH₃ H Br CF₂CF₃ H CF₃ O CH₂CF₃ P646 H CH₃ H Br CF₂CF₃ H CH₃ O CH₂CF₃ P647 H CH₃ H Br CF₃ H H O CH₂CF₃ P648 H CH₃ H Br CF₃ H Br O CH₂CF₃ P649 H CH₃ H Br CF₃ H Cl O CH₂CF₃ P650 H CH₃ H Br CF₃ H CF₃ O CH₂CF₃ P651 H CH₃ H Br CF₃ H CH₃ O CH₂CF₃ P652 H CH₃ H Br CF₃ H H S CH₂CF₃ P653 H CH₃ H Br CF₃ H Br S CH₂CF₃ P654 H CH₃ H Br CF₃ H Cl S CH₂CF₃ P655 H CH₃ H Br CF₃ H CF₃ S CH₂CF₃ P656 H CH₃ H Br CF₃ H CH₃ S CH₂CF₃ P657 H CH₃ H Br CF₃ H H O CH₂CHF₂ P658 H CH₃ H Br CF₃ H Br O CH₂CHF₂ P659 H CH₃ H Br CF₃ H Cl O CH₂CHF₂ P660 H CH₃ H Br CF₃ H CF₃ O CH₂CHF₂ P661 H CH₃ H Br CF₃ H CH₃ O CH₂CHF₂ P662 H CH₃ H Br CF₃ H H O CH₂CH₂F P663 H CH₃ H Br CF₃ H Br O CH₂CH₂F P664 H CH₃ H Br CF₃ H Cl O CH₂CH₂F P665 H CH₃ H Br CF₃ H CF₃ O CH₂CH₂F P666 H CH₃ H Br CF₃ H CH₃ O CH₂CH₂F P667 H CH₃ H Br CF₃ H H O CH₂CH₃ P668 H CH₃ H Br CF₃ H Br O CH₂CH₃ P669 H CH₃ H Br CF₃ H Cl O CH₂CH₃ P670 H CH₃ H Br CF₃ H CF₃ O CH₂CH₃ P671 H CH₃ H Br CF₃ H CH₃ O CH₂CH₃ P672 H CH₃ H Br CF₃ H H O CH(CH₃)CF₃ P673 H CH₃ H Br CF₃ H Br O CH(CH₃)CF₃ P674 H CH₃ H Br CF₃ H Cl O CH(CH₃)CF₃ P675 H CH₃ H Br CF₃ H CF₃ O CH(CH₃)CF₃ P676 H CH₃ H Br CF₃ H CH₃ O CH(CH₃)CF₃ P677 H CH₃ H Br CF₃ H H O CH₂CH₂CF₃ P678 H CH₃ H Br CF₃ H Br O CH₂CH₂CF₃ P679 H CH₃ H Br CF₃ H Cl O CH₂CH₂CF₃ P680 H CH₃ H Br CF₃ H CF₃ O CH₂CH₂CF₃ P681 H CH₃ H Br CF₃ H CH₃ O CH₂CH₂CF₃ P682 H H F CH₃ CF₃ CF₃ H O CH₂CF₃ P683 H H F CH₃ CF₃ CF₃ Br O CH₂CF₃ P684 H H F CH₃ CF₃ CF₃ Cl O CH₂CF₃ P685 H H F CH₃ CF₃ CF₃ CF₃ O CH₂CF₃ P686 H H F CH₃ CF₃ CF₃ CH₃ O CH₂CF₃ P687 H H F CH₃ CF₂CF₃ H H O CH₂CF₃ P688 H H F CH₃ CF₂CF₃ H Br O CH₂CF₃ P689 H H F CH₃ CF₂CF₃ H Cl O CH₂CF₃ P690 H H F CH₃ CF₂CF₃ H CF₃ O CH₂CF₃ P691 H H F CH₃ CF₂CF₃ H CH₃ O CH₂CF₃ P692 H H F CH₃ CF₃ H H O CH₂CF₃ P693 H H F CH₃ CF₃ H Br O CH₂CF₃ P694 H H F CH₃ CF₃ H Cl O CH₂CF₃ P695 H H F CH₃ CF₃ H CF₃ O CH₂CF₃ P696 H H F CH₃ CF₃ H CH₃ O CH₂CF₃ P697 H H F CH₃ CF₃ H H S CH₂CF₃ P698 H H F CH₃ CF₃ H Br S CH₂CF₃ P699 H H F CH₃ CF₃ H Cl S CH₂CF₃ P700 H H F CH₃ CF₃ H CF₃ S CH₂CF₃ P701 H H F CH₃ CF₃ H CH₃ S CH₂CF₃ P702 H H F CH₃ CF₃ H H O CH₂CHF₂ P703 H H F CH₃ CF₃ H Br O CH₂CHF₂ P704 H H F CH₃ CF₃ H Cl O CH₂CHF₂ P705 H H F CH₃ CF₃ H CF₃ O CH₂CHF₂ P706 H H F CH₃ CF₃ H CH₃ O CH₂CHF₂ P707 H H F CH₃ CF₃ H H O CH₂CH₂F P708 H H F CH₃ CF₃ H Br O CH₂CH₂F P709 H H F CH₃ CF₃ H Cl O CH₂CH₂F P710 H H F CH₃ CF₃ H CF₃ O CH₂CH₂F P711 H H F CH₃ CF₃ H CH₃ O CH₂CH₂F P712 H H F CH₃ CF₃ H H O CH₂CH₃ P713 H H F CH₃ CF₃ H Br O CH₂CH₃ P714 H H F CH₃ CF₃ H Cl O CH₂CH₃ P715 H H F CH₃ CF₃ H CF₃ O CH₂CH₃ P716 H H F CH₃ CF₃ H CH₃ O CH₂CH₃ P717 H H F CH₃ CF₃ H H O CH(CH₃)CF₃ P718 H H F CH₃ CF₃ H Br O CH(CH₃)CF₃ P719 H H F CH₃ CF₃ H Cl O CH(CH₃)CF₃ P720 H H F CH₃ CF₃ H CF₃ O CH(CH₃)CF₃ P721 H H F CH₃ CF₃ H CH₃ O CH(CH₃)CF₃ P722 H H F CH₃ CF₃ H H O CH₂CH₂CF₃ P723 H H F CH₃ CF₃ H Br O CH₂CH₂CF₃ P724 H H F CH₃ CF₃ H Cl O CH₂CH₂CF₃ P725 H H F CH₃ CF₃ H CF₃ O CH₂CH₂CF₃ P726 H H F CH₃ CF₃ H CH₃ O CH₂CH₂CF₃ P727 H H F Cl CF₃ CF₃ H O CH₂CF₃ P728 H H F Cl CF₃ CF₃ Br O CH₂CF₃ P729 H H F Cl CF₃ CF₃ Cl O CH₂CF₃ P730 H H F Cl CF₃ CF₃ CF₃ O CH₂CF₃ P731 H H F Cl CF₃ CF₃ CH₃ O CH₂CF₃ P732 H H F Cl CF₂CF₃ H H O CH₂CF₃ P733 H H F Cl CF₂CF₃ H Br O CH₂CF₃ P734 H H F Cl CF₂CF₃ H Cl O CH₂CF₃ P735 H H F Cl CF₂CF₃ H CF₃ O CH₂CF₃ P736 H H F Cl CF₂CF₃ H CH₃ O CH₂CF₃ P737 H H F Cl CF₃ H H O CH₂CF₃ P738 H H F Cl CF₃ H Br O CH₂CF₃ P739 H H F Cl CF₃ H Cl O CH₂CF₃ P740 H H F Cl CF₃ H CF₃ O CH₂CF₃ P741 H H F Cl CF₃ H CH₃ O CH₂CF₃ P742 H H F Cl CF₃ H H S CH₂CF₃ P743 H H F Cl CF₃ H Br S CH₂CF₃ P744 H H F Cl CF₃ H Cl S CH₂CF₃ P745 H H F Cl CF₃ H CF₃ S CH₂CF₃ P746 H H F Cl CF₃ H CH₃ S CH₂CF₃ P747 H H F Cl CF₃ H H O CH₂CHF₂ P748 H H F Cl CF₃ H Br O CH₂CHF₂ P749 H H F Cl CF₃ H Cl O CH₂CHF₂ P750 H H F Cl CF₃ H CF₃ O CH₂CHF₂ P751 H H F Cl CF₃ H CH₃ O CH₂CHF₂ P752 H H F Cl CF₃ H H O CH₂CH₂F P753 H H F Cl CF₃ H Br O CH₂CH₂F P754 H H F Cl CF₃ H Cl O CH₂CH₂F P755 H H F Cl CF₃ H CF₃ O CH₂CH₂F P756 H H F Cl CF₃ H CH₃ O CH₂CH₂F P757 H H F Cl CF₃ H H O CH₂CH₃ P758 H H F Cl CF₃ H Br O CH₂CH₃ P759 H H F Cl CF₃ H Cl O CH₂CH₃ P760 H H F Cl CF₃ H CF₃ O CH₂CH₃ P761 H H F Cl CF₃ H CH₃ O CH₂CH₃ P762 H H F Cl CF₃ H H O CH(CH₃)CF₃ P763 H H F Cl CF₃ H Br O CH(CH₃)CF₃ P764 H H F Cl CF₃ H Cl O CH(CH₃)CF₃ P765 H H F Cl CF₃ H CF₃ O CH(CH₃)CF₃ P766 H H F Cl CF₃ H CH₃ O CH(CH₃)CF₃ P767 H H F Cl CF₃ H H O CH₂CH₂CF₃ P768 H H F Cl CF₃ H Br O CH₂CH₂CF₃ P769 H H F Cl CF₃ H Cl O CH₂CH₂CF₃ P770 H H F Cl CF₃ H CF₃ O CH₂CH₂CF₃ P771 H H F Cl CF₃ H CH₃ O CH₂CH₂CF₃ P772 H F F F CF₃ CF₃ H O CH₂CF₃ P773 H F F F CF₃ CF₃ Br O CH₂CF₃ P774 H F F F CF₃ CF₃ Cl O CH₂CF₃ P775 H F F F CF₃ CF₃ CF₃ O CH₂CF₃ P776 H F F F CF₃ CF₃ CH₃ O CH₂CF₃ P777 H F F F CF₂CF₃ H H O CH₂CF₃ P778 H F F F CF₂CF₃ H Br O CH₂CF₃ P779 H F F F CF₂CF₃ H Cl O CH₂CF₃ P780 H F F F CF₂CF₃ H CF₃ O CH₂CF₃ P781 H F F F CF₂CF₃ H CH₃ O CH₂CF₃ P782 H F F F CF₃ H H O CH₂CF₃ P783 H F F F CF₃ H Br O CH₂CF₃ P784 H F F F CF₃ H Cl O CH₂CF₃ P785 H F F F CF₃ H CF₃ O CH₂CF₃ P786 H F F F CF₃ H CH₃ O CH₂CF₃ P787 H F F F CF₃ H H S CH₂CF₃ P788 H F F F CF₃ H Br S CH₂CF₃ P789 H F F F CF₃ H Cl S CH₂CF₃ P790 H F F F CF₃ H CF₃ S CH₂CF₃ P791 H F F F CF₃ H CH₃ S CH₂CF₃ P792 H F F F CF₃ H H O CH₂CHF₂ P793 H F F F CF₃ H Br O CH₂CHF₂ P794 H F F F CF₃ H Cl O CH₂CHF₂ P795 H F F F CF₃ H CF₃ O CH₂CHF₂ P796 H F F F CF₃ H CH₃ O CH₂CHF₂ P797 H F F F CF₃ H H O CH₂CH₂F P798 H F F F CF₃ H Br O CH₂CH₂F P799 H F F F CF₃ H Cl O CH₂CH₂F P800 H F F F CF₃ H CF₃ O CH₂CH₂F P801 H F F F CF₃ H CH₃ O CH₂CH₂F P802 H F F F CF₃ H H O CH₂CH₃ P803 H F F F CF₃ H Br O CH₂CH₃ P804 H F F F CF₃ H Cl O CH₂CH₃ P805 H F F F CF₃ H CF₃ O CH₂CH₃ P806 H F F F CF₃ H CH₃ O CH₂CH₃ P807 H F F F CF₃ H H O CH(CH₃)CF₃ P808 H F F F CF₃ H Br O CH(CH₃)CF₃ P809 H F F F CF₃ H Cl O CH(CH₃)CF₃ P810 H F F F CF₃ H CF₃ O CH(CH₃)CF₃ P811 H F F F CF₃ H CH₃ O CH(CH₃)CF₃ P812 H F F F CF₃ H H O CH₂CH₂CF₃ P813 H F F F CF₃ H Br O CH₂CH₂CF₃ P814 H F F F CF₃ H Cl O CH₂CH₂CF₃ P815 H F F F CF₃ H CF₃ O CH₂CH₂CF₃ P816 H F F F CF₃ H CH₃ O CH₂CH₂CF₃ P817 H CF₃ H CF₃ CF₃ CF₃ H O CH₂CF₃ P818 H CF₃ H CF₃ CF₃ CF₃ Br O CH₂CF₃ P819 H CF₃ H CF₃ CF₃ CF₃ Cl O CH₂CF₃ P820 H CF₃ H CF₃ CF₃ CF₃ CF₃ O CH₂CF₃ P821 H CF₃ H CF₃ CF₃ CF₃ CH₃ O CH₂CF₃ P822 H CF₃ H CF₃ CF₂CF₃ H H O CH₂CF₃ P823 H CF₃ H CF₃ CF₂CF₃ H Br O CH₂CF₃ P824 H CF₃ H CF₃ CF₂CF₃ H Cl O CH₂CF₃ P825 H CF₃ H CF₃ CF₂CF₃ H CF₃ O CH₂CF₃ P826 H CF₃ H CF₃ CF₂CF₃ H CH₃ O CH₂CF₃ P827 H CF₃ H CF₃ CF₃ H H O CH₂CF₃ P828 H CF₃ H CF₃ CF₃ H Br O CH₂CF₃ P829 H CF₃ H CF₃ CF₃ H Cl O CH₂CF₃ P830 H CF₃ H CF₃ CF₃ H CF₃ O CH₂CF₃ P831 H CF₃ H CF₃ CF₃ H CH₃ O CH₂CF₃ P832 H CF₃ H CF₃ CF₃ H H S CH₂CF₃ P833 H CF₃ H CF₃ CF₃ H Br S CH₂CF₃ P834 H CF₃ H CF₃ CF₃ H Cl S CH₂CF₃ P835 H CF₃ H CF₃ CF₃ H CF₃ S CH₂CF₃ P836 H CF₃ H CF₃ CF₃ H CH₃ S CH₂CF₃ P837 H CF₃ H CF₃ CF₃ H H O CH₂CHF₂ P838 H CF₃ H CF₃ CF₃ H Br O CH₂CHF₂ P839 H CF₃ H CF₃ CF₃ H Cl O CH₂CHF₂ P840 H CF₃ H CF₃ CF₃ H CF₃ O CH₂CHF₂ P841 H CF₃ H CF₃ CF₃ H CH₃ O CH₂CHF₂ P842 H CF₃ H CF₃ CF₃ H H O CH₂CH₂F P843 H CF₃ H CF₃ CF₃ H Br O CH₂CH₂F P844 H CF₃ H CF₃ CF₃ H Cl O CH₂CH₂F P845 H CF₃ H CF₃ CF₃ H CF₃ O CH₂CH₂F P846 H CF₃ H CF₃ CF₃ H CH₃ O CH₂CH₂F P847 H CF₃ H CF₃ CF₃ H H O CH₂CH₃ P848 H CF₃ H CF₃ CF₃ H Br O CH₂CH₃ P849 H CF₃ H CF₃ CF₃ H Cl O CH₂CH₃ P850 H CF₃ H CF₃ CF₃ H CF₃ O CH₂CH₃ P851 H CF₃ H CF₃ CF₃ H CH₃ O CH₂CH₃ P852 H CF₃ H CF₃ CF₃ H H O CH(CH₃)CF₃ P853 H CF₃ H CF₃ CF₃ H Br O CH(CH₃)CF₃ P854 H CF₃ H CF₃ CF₃ H Cl O CH(CH₃)CF₃ P855 H CF₃ H CF₃ CF₃ H CF₃ O CH(CH₃)CF₃ P856 H CF₃ H CF₃ CF₃ H CH₃ O CH(CH₃)CF₃ P857 H CF₃ H CF₃ CF₃ H H O CH₂CH₂CF₃ P858 H CF₃ H CF₃ CF₃ H Br O CH₂CH₂CF₃ P859 H CF₃ H CF₃ CF₃ H Cl O CH₂CH₂CF₃ P860 H CF₃ H CF₃ CF₃ H CF₃ O CH₂CH₂CF₃ P861 H CF₃ H CF₃ CF₃ H CH₃ O CH₂CH₂CF₃ P862 H F H CF₃ CF₃ CF₃ H O CH₂CF₃ P863 H F H CF₃ CF₃ CF₃ Br O CH₂CF₃ P864 H F H CF₃ CF₃ CF₃ Cl O CH₂CF₃ P865 H F H CF₃ CF₃ CF₃ CF₃ O CH₂CF₃ P866 H F H CF₃ CF₃ CF₃ CH₃ O CH₂CF₃ P867 H F H CF₃ CF₂CF₃ H H O CH₂CF₃ P868 H F H CF₃ CF₂CF₃ H Br O CH₂CF₃ P869 H F H CF₃ CF₂CF₃ H Cl O CH₂CF₃ P870 H F H CF₃ CF₂CF₃ H CF₃ O CH₂CF₃ P871 H F H CF₃ CF₂CF₃ H CH₃ O CH₂CF₃ P872 H F H CF₃ CF₃ H H O CH₂CF₃ P873 H F H CF₃ CF₃ H Br O CH₂CF₃ P874 H F H CF₃ CF₃ H Cl O CH₂CF₃ P875 H F H CF₃ CF₃ H CF₃ O CH₂CF₃ P876 H F H CF₃ CF₃ H CH₃ O CH₂CF₃ P877 H F H CF₃ CF₃ H H S CH₂CF₃ P878 H F H CF₃ CF₃ H Br S CH₂CF₃ P879 H F H CF₃ CF₃ H Cl S CH₂CF₃ P880 H F H CF₃ CF₃ H CF₃ S CH₂CF₃ P881 H F H CF₃ CF₃ H CH₃ S CH₂CF₃ P882 H F H CF₃ CF₃ H H O CH₂CHF₂ P883 H F H CF₃ CF₃ H Br O CH₂CHF₂ P884 H F H CF₃ CF₃ H Cl O CH₂CHF₂ P885 H F H CF₃ CF₃ H CF₃ O CH₂CHF₂ P886 H F H CF₃ CF₃ H CH₃ O CH₂CHF₂ P887 H F H CF₃ CF₃ H H O CH₂CH₂F P888 H F H CF₃ CF₃ H Br O CH₂CH₂F P889 H F H CF₃ CF₃ H Cl O CH₂CH₂F P890 H F H CF₃ CF₃ H CF₃ O CH₂CH₂F P891 H F H CF₃ CF₃ H CH₃ O CH₂CH₂F P892 H F H CF₃ CF₃ H H O CH₂CH₃ P893 H F H CF₃ CF₃ H Br O CH₂CH₃ P894 H F H CF₃ CF₃ H Cl O CH₂CH₃ P895 H F H CF₃ CF₃ H CF₃ O CH₂CH₃ P896 H F H CF₃ CF₃ H CH₃ O CH₂CH₃ P897 H F H CF₃ CF₃ H H O CH(CH₃)CF₃ P898 H F H CF₃ CF₃ H Br O CH(CH₃)CF₃ P899 H F H CF₃ CF₃ H Cl O CH(CH₃)CF₃ P900 H F H CF₃ CF₃ H CF₃ O CH(CH₃)CF₃ P901 H F H CF₃ CF₃ H CH₃ O CH(CH₃)CF₃ P902 H F H CF₃ CF₃ H H O CH₂CH₂CF₃ P903 H F H CF₃ CF₃ H Br O CH₂CH₂CF₃ P904 H F H CF₃ CF₃ H Cl O CH₂CH₂CF₃ P905 H F H CF₃ CF₃ H CF₃ O CH₂CH₂CF₃ P906 H F H CF₃ CF₃ H CH₃ O CH₂CH₂CF₃ P907 H Cl H CF₃ CF₃ CF₃ H O CH₂CF₃ P908 H Cl H CF₃ CF₃ CF₃ Br O CH₂CF₃ P909 H Cl H CF₃ CF₃ CF₃ Cl O CH₂CF₃ P910 H Cl H CF₃ CF₃ CF₃ CF₃ O CH₂CF₃ P911 H Cl H CF₃ CF₃ CF₃ CH₃ O CH₂CF₃ P912 H Cl H CF₃ CF₂CF₃ H H O CH₂CF₃ P913 H Cl H CF₃ CF₂CF₃ H Br O CH₂CF₃ P914 H Cl H CF₃ CF₂CF₃ H Cl O CH₂CF₃ P915 H Cl H CF₃ CF₂CF₃ H CF₃ O CH₂CF₃ P916 H Cl H CF₃ CF₂CF₃ H CH₃ O CH₂CF₃ P917 H Cl H CF₃ CF₃ H H O CH₂CF₃ P918 H Cl H CF₃ CF₃ H Br O CH₂CF₃ P919 H Cl H CF₃ CF₃ H Cl O CH₂CF₃ P920 H Cl H CF₃ CF₃ H CF₃ O CH₂CF₃ P921 H Cl H CF₃ CF₃ H CH₃ O CH₂CF₃ P922 H Cl H CF₃ CF₃ H H S CH₂CF₃ P923 H Cl H CF₃ CF₃ H Br S CH₂CF₃ P924 H Cl H CF₃ CF₃ H Cl S CH₂CF₃ P925 H Cl H CF₃ CF₃ H CF₃ S CH₂CF₃ P926 H Cl H CF₃ CF₃ H CH₃ S CH₂CF₃ P927 H Cl H CF₃ CF₃ H H O CH₂CHF₂ P928 H Cl H CF₃ CF₃ H Br O CH₂CHF₂ P929 H Cl H CF₃ CF₃ H Cl O CH₂CHF₂ P930 H Cl H CF₃ CF₃ H CF₃ O CH₂CHF₂ P931 H Cl H CF₃ CF₃ H CH₃ O CH₂CHF₂ P932 H Cl H CF₃ CF₃ H H O CH₂CH₂F P933 H Cl H CF₃ CF₃ H Br O CH₂CH₂F P934 H Cl H CF₃ CF₃ H Cl O CH₂CH₂F P935 H Cl H CF₃ CF₃ H CF₃ O CH₂CH₂F P936 H Cl H CF₃ CF₃ H CH₃ O CH₂CH₂F P937 H Cl H CF₃ CF₃ H H O CH₂CH₃ P938 H Cl H CF₃ CF₃ H Br O CH₂CH₃ P939 H Cl H CF₃ CF₃ H Cl O CH₂CH₃ P940 H Cl H CF₃ CF₃ H CF₃ O CH₂CH₃ P941 H Cl H CF₃ CF₃ H CH₃ O CH₂CH₃ P942 H Cl H CF₃ CF₃ H H O CH(CH₃)CF₃ P943 H Cl H CF₃ CF₃ H Br O CH(CH₃)CF₃ P944 H Cl H CF₃ CF₃ H Cl O CH(CH₃)CF₃ P945 H Cl H CF₃ CF₃ H CF₃ O CH(CH₃)CF₃ P946 H Cl H CF₃ CF₃ H CH₃ O CH(CH₃)CF₃ P947 H Cl H CF₃ CF₃ H H O CH₂CH₂CF₃ P948 H Cl H CF₃ CF₃ H Br O CH₂CH₂CF₃ P949 H Cl H CF₃ CF₃ H Cl O CH₂CH₂CF₃ P950 H Cl H CF₃ CF₃ H CF₃ O CH₂CH₂CF₃ P951 H Cl H CF₃ CF₃ H CH₃ O CH₂CH₂CF₃ P952 H H F CF₃ CF₃ CF₃ H O CH₂CF₃ P953 H H F CF₃ CF₃ CF₃ Br O CH₂CF₃ P954 H H F CF₃ CF₃ CF₃ Cl O CH₂CF₃ P955 H H F CF₃ CF₃ CF₃ CF₃ O CH₂CF₃ P956 H H F CF₃ CF₃ CF₃ CH₃ O CH₂CF₃ P957 H H F CF₃ CF₂CF₃ H H O CH₂CF₃ P958 H H F CF₃ CF₂CF₃ H Br O CH₂CF₃ P959 H H F CF₃ CF₂CF₃ H Cl O CH₂CF₃ P960 H H F CF₃ CF₂CF₃ H CF₃ O CH₂CF₃ P961 H H F CF₃ CF₂CF₃ H CH₃ O CH₂CF₃ P962 H H F CF₃ CF₃ H H O CH₂CF₃ P963 H H F CF₃ CF₃ H Br O CH₂CF₃ P964 H H F CF₃ CF₃ H Cl O CH₂CF₃ P965 H H F CF₃ CF₃ H CF₃ O CH₂CF₃ P966 H H F CF₃ CF₃ H CH₃ O CH₂CF₃ P967 H H F CF₃ CF₃ H H S CH₂CF₃ P968 H H F CF₃ CF₃ H Br S CH₂CF₃ P969 H H F CF₃ CF₃ H Cl S CH₂CF₃ P970 H H F CF₃ CF₃ H CF₃ S CH₂CF₃ P971 H H F CF₃ CF₃ H CH₃ S CH₂CF₃ P972 H H F CF₃ CF₃ H H O CH₂CHF₂ P973 H H F CF₃ CF₃ H Br O CH₂CHF₂ P974 H H F CF₃ CF₃ H Cl O CH₂CHF₂ P975 H H F CF₃ CF₃ H CF₃ O CH₂CHF₂ P976 H H F CF₃ CF₃ H CH₃ O CH₂CHF₂ P977 H H F CF₃ CF₃ H H O CH₂CH₂F P978 H H F CF₃ CF₃ H Br O CH₂CH₂F P979 H H F CF₃ CF₃ H Cl O CH₂CH₂F P980 H H F CF₃ CF₃ H CF₃ O CH₂CH₂F P981 H H F CF₃ CF₃ H CH₃ O CH₂CH₂F P982 H H F CF₃ CF₃ H H O CH₂CH₃ P983 H H F CF₃ CF₃ H Br O CH₂CH₃ P984 H H F CF₃ CF₃ H Cl O CH₂CH₃ P985 H H F CF₃ CF₃ H CF₃ O CH₂CH₃ P986 H H F CF₃ CF₃ H CH₃ O CH₂CH₃ P987 H H F CF₃ CF₃ H H O CH(CH₃)CF₃ P988 H H F CF₃ CF₃ H Br O CH(CH₃)CF₃ P989 H H F CF₃ CF₃ H Cl O CH(CH₃)CF₃ P990 H H F CF₃ CF₃ H CF₃ O CH(CH₃)CF₃ P991 H H F CF₃ CF₃ H CH₃ O CH(CH₃)CF₃ P992 H H F CF₃ CF₃ H H O CH₂CH₂CF₃ P993 H H F CF₃ CF₃ H Br O CH₂CH₂CF₃ P994 H H F CF₃ CF₃ H Cl O CH₂CH₂CF₃ P995 H H F CF₃ CF₃ H CF₃ O CH₂CH₂CF₃ P996 H H F CF₃ CF₃ H CH₃ O CH₂CH₂CF₃ P997 H Cl Cl Cl CF₃ CF₃ H O CH₂CF₃ P998 H Cl Cl Cl CF₃ CF₃ Br O CH₂CF₃ P999 H Cl Cl Cl CF₃ CF₃ Cl O CH₂CF₃ P1000 H Cl Cl Cl CF₃ CF₃ CF₃ O CH₂CF₃ P1001 H Cl Cl Cl CF₃ CF₃ CH₃ O CH₂CF₃ P1002 H Cl Cl Cl CF₂CF₃ H H O CH₂CF₃ P1003 H Cl Cl Cl CF₂CF₃ H Br O CH₂CF₃ P1004 H Cl Cl Cl CF₂CF₃ H Cl O CH₂CF₃ P1005 H Cl Cl Cl CF₂CF₃ H CF₃ O CH₂CF₃ P1006 H Cl Cl Cl CF₂CF₃ H CH₃ O CH₂CF₃ P1007 H Cl Cl Cl CF₃ H H O CH₂CF₃ P1008 H Cl Cl Cl CF₃ H H S CH₂CF₃ P1009 H Cl Cl Cl CF₃ H Br S CH₂CF₃ P1010 H Cl Cl Cl CF₃ H Cl S CH₂CF₃ P1011 H Cl Cl Cl CF₃ H CH₃ S CH₂CF₃ P1012 H Cl Cl Cl CF₃ H H O CH₂CHF₂ P1013 H Cl Cl Cl CF₃ H Br O CH₂CHF₂ P1014 H Cl Cl Cl CF₃ H Cl O CH₂CHF₂ P1015 H Cl Cl Cl CF₃ H CF₃ O CH₂CHF₂ P1016 H Cl Cl Cl CF₃ H CH₃ O CH₂CHF₂ P1017 H Cl Cl Cl CF₃ H H O CH₂CH₂F P1018 H Cl Cl Cl CF₃ H Br O CH₂CH₂F P1019 H Cl Cl Cl CF₃ H Cl O CH₂CH₂F P1020 H Cl Cl Cl CF₃ H CF₃ O CH₂CH₂F P1021 H Cl Cl Cl CF₃ H CH₃ O CH₂CH₂F P1022 H Cl Cl Cl CF₃ H H O CH₂CH₃ P1023 H Cl Cl Cl CF₃ H Br O CH₂CH₃ P1024 H Cl Cl Cl CF₃ H Cl O CH₂CH₃ P1025 H Cl Cl Cl CF₃ H CF₃ O CH₂CH₃ P1026 H Cl Cl Cl CF₃ H CH₃ O CH₂CH₃ P1027 H Cl Cl Cl CF₃ H H O CH(CH₃)CF₃ P1028 H Cl Cl Cl CF₃ H Br O CH(CH₃)CF₃ P1029 H Cl Cl Cl CF₃ H Cl O CH(CH₃)CF₃ P1030 H Cl Cl Cl CF₃ H CF₃ O CH(CH₃)CF₃ P1031 H Cl Cl Cl CF₃ H CH₃ O CH(CH₃)CF₃ P1032 H Cl Cl Cl CF₃ H H O CH₂CH₂CF₃ P1033 H Cl Cl Cl CF₃ H Br O CH₂CH₂CF₃ P1034 H Cl Cl Cl CF₃ H Cl O CH₂CH₂CF₃ P1035 H Cl Cl Cl CF₃ H CF₃ O CH₂CH₂CF₃ P1036 H Cl Cl Cl CF₃ H CH₃ O CH₂CH₂CF₃ P1037 H Cl H Cl CF₃ CF₃ H O CH₂CF₃ P1038 H Cl H Cl CF₃ CF₃ Br O CH₂CF₃ P1039 H Cl H Cl CF₃ CF₃ Cl O CH₂CF₃ P1040 H Cl H Cl CF₃ CF₃ CF₃ O CH₂CF₃ P1041 H Cl H Cl CF₃ CF₃ CH₃ O CH₂CF₃ P1042 H Cl H Cl CF₂CF₃ H H O CH₂CF₃ P1043 H Cl H Cl CF₂CF₃ H Br O CH₂CF₃ P1044 H Cl H Cl CF₂CF₃ H Cl O CH₂CF₃ P1045 H Cl H Cl CF₂CF₃ H CF₃ O CH₂CF₃ P1046 H Cl H Cl CF₂CF₃ H CH₃ O CH₂CF₃ P1047 H Cl H Cl CF₃ H H O CH₂CF₃ P1048 H Cl H Cl CF₃ H Br O CH₂CF₃ P1049 H Cl H Cl CF₃ H Cl O CH₂CF₃ P1050 H Cl H Cl CF₃ H CF₃ O CH₂CF₃ P1051 H Cl H Cl CF₃ H CH₃ O CH₂CF₃ P1052 H Cl H Cl CF₃ H H S CH₂CF₃ P1053 H Cl H Cl CF₃ H Br S CH₂CF₃ P1054 H Cl H Cl CF₃ H Cl S CH₂CF₃ P1055 H Cl H Cl CF₃ H CF₃ S CH₂CF₃ P1056 H Cl H Cl CF₃ H CH₃ S CH₂CF₃ P1057 H Cl H Cl CF₃ H H O CH₂CHF₂ P1058 H Cl H Cl CF₃ H Br O CH₂CHF₂ P1059 H Cl H Cl CF₃ H Cl O CH₂CHF₂ P1060 H Cl H Cl CF₃ H CF₃ O CH₂CHF₂ P1061 H Cl H Cl CF₃ H CH₃ O CH₂CHF₂ P1062 H Cl H Cl CF₃ H H O CH₂CH₂F P1063 H Cl H Cl CF₃ H Br O CH₂CH₂F P1064 H Cl H Cl CF₃ H Cl O CH₂CH₂F P1065 H Cl H Cl CF₃ H CF₃ O CH₂CH₂F P1066 H Cl H Cl CF₃ H CH₃ O CH₂CH₂F P1067 H Cl H Cl CF₃ H H O CH₂CH₃ P1068 H Cl H Cl CF₃ H Br O CH₂CH₃ P1069 H Cl H Cl CF₃ H Cl O CH₂CH₃ P1070 H Cl H Cl CF₃ H CF₃ O CH₂CH₃ P1071 H Cl H Cl CF₃ H CH₃ O CH₂CH₃ P1072 H Cl H Cl CF₃ H H O CH(CH₃)CF₃ P1073 H Cl H Cl CF₃ H Br O CH(CH₃)CF₃ P1074 H Cl H Cl CF₃ H Cl O CH(CH₃)CF₃ P1075 H Cl H Cl CF₃ H CF₃ O CH(CH₃)CF₃ P1076 H Cl H Cl CF₃ H CH₃ O CH(CH₃)CF₃ P1077 H Cl H Cl CF₃ H H O CH₂CH₂CF₃ P1078 H Cl H Cl CF₃ H Br O CH₂CH₂CF₃ P1079 H Cl H Cl CF₃ H Cl O CH₂CH₂CF₃ P1080 H Cl H Cl CF₃ H CF₃ O CH₂CH₂CF₃ P1081 H Cl H Cl CF₃ H CH₃ O CH₂CH₂CF₃ P1082 H H Cl Cl CF₃ CF₃ H O CH₂CF₃ P1083 H H Cl Cl CF₃ CF₃ Br O CH₂CF₃ P1084 H H Cl Cl CF₃ CF₃ Cl O CH₂CF₃ P1085 H H Cl Cl CF₃ CF₃ CF₃ O CH₂CF₃ P1086 H H Cl Cl CF₃ CF₃ CH₃ O CH₂CF₃ P1087 H H Cl Cl CF₂CF₃ H H O CH₂CF₃ P1088 H H Cl Cl CF₂CF₃ H Br O CH₂CF₃ P1089 H H Cl Cl CF₂CF₃ H Cl O CH₂CF₃ P1090 H H Cl Cl CF₂CF₃ H CF₃ O CH₂CF₃ P1091 H H Cl Cl CF₂CF₃ H CH₃ O CH₂CF₃ P1092 H H Cl Cl CF₃ H H O CH₂CF₃ P1093 H H Cl Cl CF₃ H Br O CH₂CF₃ P1094 H H Cl Cl CF₃ H Cl O CH₂CF₃ P1095 H H Cl Cl CF₃ H CF₃ O CH₂CF₃ P1096 H H Cl Cl CF₃ H CH₃ O CH₂CF₃ P1097 H H Cl Cl CF₃ H H S CH₂CF₃ P1098 H H Cl Cl CF₃ H Br S CH₂CF₃ P1099 H H Cl Cl CF₃ H Cl S CH₂CF₃ P1100 H H Cl Cl CF₃ H CF₃ S CH₂CF₃ P1101 H H Cl Cl CF₃ H CH₃ S CH₂CF₃ P1102 H H Cl Cl CF₃ H H O CH₂CHF₂ P1103 H H Cl Cl CF₃ H Br O CH₂CHF₂ P1104 H H Cl Cl CF₃ H Cl O CH₂CHF₂ P1105 H H Cl Cl CF₃ H CF₃ O CH₂CHF₂ P1106 H H Cl Cl CF₃ H CH₃ O CH₂CHF₂ P1107 H H Cl Cl CF₃ H H O CH₂CH₂F P1108 H H Cl Cl CF₃ H Br O CH₂CH₂F P1109 H H Cl Cl CF₃ H Cl O CH₂CH₂F P1110 H H Cl Cl CF₃ H CF₃ O CH₂CH₂F P1111 H H Cl Cl CF₃ H CH₃ O CH₂CH₂F P1112 H H Cl Cl CF₃ H H O CH₂CH₃ P1113 H H Cl Cl CF₃ H Br O CH₂CH₃ P1114 H H Cl Cl CF₃ H Cl O CH₂CH₃ P1115 H H Cl Cl CF₃ H CF₃ O CH₂CH₃ P1116 H H Cl Cl CF₃ H CH₃ O CH₂CH₃ P1117 H H Cl Cl CF₃ H H O CH(CH₃)CF₃ P1118 H H Cl Cl CF₃ H Br O CH(CH₃)CF₃ P1119 H H Cl Cl CF₃ H Cl O CH(CH₃)CF₃ P1120 H H Cl Cl CF₃ H CF₃ O CH(CH₃)CF₃ P1121 H H Cl Cl CF₃ H CH₃ O CH(CH₃)CF₃ P1122 H H Cl Cl CF₃ H H O CH₂CH₂CF₃ P1123 H H Cl Cl CF₃ H Br O CH₂CH₂CF₃ P1124 H H Cl Cl CF₃ H Cl O CH₂CH₂CF₃ P1125 H H Cl Cl CF₃ H CF₃ O CH₂CH₂CF₃ P1126 H H Cl Cl CF₃ H CH₃ O CH₂CH₂CF₃ P1127 H Cl F Cl CF₃ CF₃ H O CH₂CF₃ P1128 H Cl F Cl CF₃ CF₃ Br O CH₂CF₃ P1129 H Cl F Cl CF₃ CF₃ Cl O CH₂CF₃ P1130 H Cl F Cl CF₃ CF₃ CF₃ O CH₂CF₃ P1131 H Cl F Cl CF₃ CF₃ CH₃ O CH₂CF₃ P1132 H Cl F Cl CF₂CF₃ H H O CH₂CF₃ P1133 H Cl F Cl CF₂CF₃ H Br O CH₂CF₃ P1134 H Cl F Cl CF₂CF₃ H Cl O CH₂CF₃ P1135 H Cl F Cl CF₂CF₃ H CF₃ O CH₂CF₃ P1136 H Cl F Cl CF₂CF₃ H CH₃ O CH₂CF₃ P1137 H Cl F Cl CF₃ H H O CH₂CF₃ P1138 H Cl F Cl CF₃ H Br O CH₂CF₃ P1139 H Cl F Cl CF₃ H Cl O CH₂CF₃ P1140 H Cl F Cl CF₃ H CF₃ O CH₂CF₃ P1141 H Cl F Cl CF₃ H CH₃ O CH₂CF₃ P1142 H Cl F Cl CF₃ H H S CH₂CF₃ P1143 H Cl F Cl CF₃ H Br S CH₂CF₃ P1144 H Cl F Cl CF₃ H Cl S CH₂CF₃ P1145 H Cl F Cl CF₃ H CF₃ S CH₂CF₃ P1146 H Cl F Cl CF₃ H CH₃ S CH₂CF₃ P1147 H Cl F Cl CF₃ H H O CH₂CHF₂ P1148 H Cl F Cl CF₃ H Br O CH₂CHF₂ P1149 H Cl F Cl CF₃ H Cl O CH₂CHF₂ P1150 H Cl F Cl CF₃ H CF₃ O CH₂CHF₂ P1151 H Cl F Cl CF₃ H CH₃ O CH₂CHF₂ P1152 H Cl F Cl CF₃ H H O CH₂CH₂F P1153 H Cl F Cl CF₃ H Br O CH₂CH₂F P1154 H Cl F Cl CF₃ H Cl O CH₂CH₂F P1155 H Cl F Cl CF₃ H CF₃ O CH₂CH₂F P1156 H Cl F Cl CF₃ H CH₃ O CH₂CH₂F P1157 H Cl F Cl CF₃ H H O CH₂CH₃ P1158 H Cl F Cl CF₃ H Br O CH₂CH₃ P1159 H Cl F Cl CF₃ H Cl O CH₂CH₃ P1160 H Cl F Cl CF₃ H CF₃ O CH₂CH₃ P1161 H Cl F Cl CF₃ H CH₃ O CH₂CH₃ P1162 H Cl F Cl CF₃ H H O CH(CH₃)CF₃ P1163 H Cl F Cl CF₃ H Br O CH(CH₃)CF₃ P1164 H Cl F Cl CF₃ H Cl O CH(CH₃)CF₃ P1165 H Cl F Cl CF₃ H CF₃ O CH(CH₃)CF₃ P1166 H Cl F Cl CF₃ H CH₃ O CH(CH₃)CF₃ P1167 H Cl F Cl CF₃ H H O CH₂CH₂CF₃ P1168 H Cl F Cl CF₃ H Br O CH₂CH₂CF₃ P1169 H Cl F Cl CF₃ H Cl O CH₂CH₂CF₃ P1170 H Cl F Cl CF₃ H CF₃ O CH₂CH₂CF₃ P1171 H Cl F Cl CF₃ H CH₃ O CH₂CH₂CF₃ P1172 H Br H Br CF₃ CF₃ H O CH₂CF₃ P1173 H Br H Br CF₃ CF₃ Br O CH₂CF₃ P1174 H Br H Br CF₃ CF₃ Cl O CH₂CF₃ P1175 H Br H Br CF₃ CF₃ CF₃ O CH₂CF₃ P1176 H Br H Br CF₃ CF₃ CH₃ O CH₂CF₃ P1177 H Br H Br CF₂CF₃ H H O CH₂CF₃ P1178 H Br H Br CF₂CF₃ H Br O CH₂CF₃ P1179 H Br H Br CF₂CF₃ H Cl O CH₂CF₃ P1180 H Br H Br CF₂CF₃ H CF₃ O CH₂CF₃ P1181 H Br H Br CF₂CF₃ H CH₃ O CH₂CF₃ P1182 H Br H Br CF₃ H H O CH₂CF₃ P1183 H Br H Br CF₃ H Br O CH₂CF₃ P1184 H Br H Br CF₃ H Cl O CH₂CF₃ P1185 H Br H Br CF₃ H CF₃ O CH₂CF₃ P1186 H Br H Br CF₃ H CH₃ O CH₂CF₃ P1187 H Br H Br CF₃ H H S CH₂CF₃ P1188 H Br H Br CF₃ H Br S CH₂CF₃ P1189 H Br H Br CF₃ H Cl S CH₂CF₃ P1190 H Br H Br CF₃ H CF₃ S CH₂CF₃ P1191 H Br H Br CF₃ H CH₃ S CH₂CF₃ P1192 H Br H Br CF₃ H H O CH₂CHF₂ P1193 H Br H Br CF₃ H Br O CH₂CHF₂ P1194 H Br H Br CF₃ H Cl O CH₂CHF₂ P1195 H Br H Br CF₃ H CF₃ O CH₂CHF₂ P1196 H Br H Br CF₃ H CH₃ O CH₂CHF₂ P1197 H Br H Br CF₃ H H O CH₂CH₂F P1198 H Br H Br CF₃ H Br O CH₂CH₂F P1199 H Br H Br CF₃ H Cl O CH₂CH₂F P1200 H Br H Br CF₃ H CF₃ O CH₂CH₂F P1201 H Br H Br CF₃ H CH₃ O CH₂CH₂F P1202 H Br H Br CF₃ H H O CH₂CH₃ P1203 H Br H Br CF₃ H Br O CH₂CH₃ P1204 H Br H Br CF₃ H Cl O CH₂CH₃ P1205 H Br H Br CF₃ H CF₃ O CH₂CH₃ P1206 H Br H Br CF₃ H CH₃ O CH₂CH₃ P1207 H Br H Br CF₃ H H O CH(CH₃)CF₃ P1208 H Br H Br CF₃ H Br O CH(CH₃)CF₃ P1209 H Br H Br CF₃ H Cl O CH(CH₃)CF₃ P1210 H Br H Br CF₃ H CF₃ O CH(CH₃)CF₃ P1211 H Br H Br CF₃ H CH₃ O CH(CH₃)CF₃ P1212 H Br H Br CF₃ H H O CH₂CH₂CF₃ P1213 H Br H Br CF₃ H Br O CH₂CH₂CF₃ P1214 H Br H Br CF₃ H Cl O CH₂CH₂CF₃ P1215 H Br H Br CF₃ H CF₃ O CH₂CH₂CF₃ P1216 H Br H Br CF₃ H CH₃ O CH₂CH₂CF₃

Example A: Bioassays on Beet Armyworm (“BAW”) and Corn Earworm (“CEW”) and Cabbage Looper (“CL”)

BAW has few effective parasites, diseases, or predators to lower its population. BAW infests many weeds, trees, grasses, legumes, and field crops. In various places, it is of economic concern upon asparagus, cotton, corn, soybeans, tobacco, alfalfa, sugar beets, peppers, tomatoes, potatoes, onions, peas, sunflowers, and citrus, among other plants. CEW is known to attack corn and tomatoes, but it also attacks artichoke, asparagus, cabbage, cantaloupe, collards, cowpeas, cucumbers, eggplant, lettuce, lima beans, melon, okra, peas, peppers, potatoes, pumpkin, snap beans, spinach, squash, sweet potatoes, and watermelon, among other plants. CEW is also known to be resistant to certain insecticides. CL is also known to be resistant to certain insecticides. Consequently, because of the above factors control of these pests is important. Furthermore, molecules that control these pests are useful in controlling other pests.

Certain molecules disclosed in this document were tested against BAW, CEW and CL using procedures described in the following examples. In the reporting of the results, the “BAW & CEW & CL Rating Table” was used (See Table Section).

Bioassays on BAW (Spodoptera exigua)

Bioassays on BAW were conducted using a 128-well diet tray assay. One to five second instar BAW larvae were placed in each well (3 mL) of the diet tray that had been previously filled with 1 mL of artificial diet to which 50 μg/cm² of the test compound (dissolved in 50 μL of 90:10 acetone-water mixture) had been applied (to each of eight wells) and then allowed to dry. Trays were covered with a clear self-adhesive cover, and held at 25° C., 14:10 light-dark for five to seven days. Percent mortality was recorded for the larvae in each well; activity in the eight wells was then averaged. The results are indicated in the tables entitled “Table 3: Assay Results Part 1” and “Table 4: Assay Results Part 2” (See Table Section).

Bioassays on CEW (Helicoverpa zea)

Bioassays on CEW were conducted using a 128-well diet tray assay. One to five second instar CEW larvae were placed in each well (3 mL) of the diet tray that had been previously filled with 1 mL of artificial diet to which 50 μg/cm² of the test compound (dissolved in 50 μL of 90:10 acetone-water mixture) had been applied (to each of eight wells) and then allowed to dry. Trays were covered with a clear self-adhesive cover, and held at 25° C., 14:10 light-dark for five to seven days. Percent mortality was recorded for the larvae in each well; activity in the eight wells was then averaged. The results are indicated in the table entitled “Table 3: Assay Results Part 1” (See Table Section).

Bioassays on CL (Trichoplusia ni)

Bioassays on CL were conducted using a 128-well diet tray assay. One to five second instar CL larvae were placed in each well (3 mL) of the diet tray that had been previously filled with 1 mL of artificial diet to which 50 μg/cm² of the test compound (dissolved in 50 μL of 90:10 acetone-water mixture) had been applied (to each of eight wells) and then allowed to dry. Trays were covered with a clear self-adhesive cover, and held at 25° C., 14:10 light-dark for five to seven days. Percent mortality was recorded for the larvae in each well; activity in the eight wells was then averaged. The results are indicated in the table entitled “Table 4: Assay Results Part 2” (See Table Section).

Example B: Bioassays on Green Peach Aphid (“GPA”) (Myzus persicae)

GPA is the most significant aphid pest of peach trees, causing decreased growth, shriveling of the leaves, and the death of various tissues. It is also hazardous because it acts as a vector for the transport of plant viruses, such as potato virus Y and potato leafroll virus to members of the nightshade/potato family Solanaceae, and various mosaic viruses to many other food crops. GPA attacks such plants as broccoli, burdock, cabbage, carrot, cauliflower, daikon, eggplant, green beans, lettuce, macadamia, papaya, peppers, sweet potatoes, tomatoes, watercress, and zucchini, among other plants. GPA also attacks many ornamental crops such as carnation, chrysanthemum, flowering white cabbage, poinsettia, and roses. GPA has developed resistance to many pesticides.

Certain molecules disclosed in this document were tested against GPA using procedures described in the following example. In the reporting of the results, the “GPA Rating Table” was used (See Table Section).

Cabbage seedlings grown in 3-inch pots, with 2-3 small (3-5 cm) true leaves, were used as test substrate. The seedlings were infested with 20-50 GPA (wingless adult and nymph stages) one day prior to chemical application. Four pots with individual seedlings were used for each treatment. Test compounds (2 mg) were dissolved in 2 mL of acetone/methanol (1:1) solvent, forming stock solutions of 1000 ppm test compound. The stock solutions were diluted 5× with 0.025% Tween 20 in H₂O to obtain the solution at 200 ppm test compound. A hand-held aspirator-type sprayer was used for spraying a solution to both sides of cabbage leaves until runoff. Reference plants (solvent check) were sprayed with the diluent only containing 20% by volume of acetone/methanol (1:1) solvent. Treated plants were held in a holding room for three days at approximately 25° C. and ambient relative humidity (RH) prior to grading. Evaluation was conducted by counting the number of live aphids per plant under a microscope. Percent Control was measured by using Abbott's correction formula (W. S. Abbott, “A Method of Computing the Effectiveness of an Insecticide” J. Econ. Entomol. 18 (1925), pp. 265-267) as follows. Corrected % Control=100*(X−Y)/X

-   -   where     -   X=No. of live aphids on solvent check plants and     -   Y=No. of live aphids on treated plants

The results are indicated in the tables entitled “Table 3: Assay Results” and “Table 4: Assay Results Part 2” (See Table Section).

Pesticidally Acceptable Acid Addition Salts, Salt Derivatives, Solvates, Ester Derivatives, Polymorphs, Isotopes and Radionuclides

Molecules of Formula One may be formulated into pesticidally acceptable acid addition salts. By way of a non-limiting example, an amine function can form salts with hydrochloric, hydrobromic, sulfuric, phosphoric, acetic, benzoic, citric, malonic, salicylic, malic, fumaric, oxalic, succinic, tartaric, lactic, gluconic, ascorbic, maleic, aspartic, benzenesulfonic, methanesulfonic, ethanesulfonic, hydroxymethanesulfonic, and hydroxyethanesulfonic acids. Additionally, by way of a non-limiting example, an acid function can form salts including those derived from alkali or alkaline earth metals and those derived from ammonia and amines. Examples of preferred cations include sodium, potassium, and magnesium.

Molecules of Formula One may be formulated into salt derivatives. By way of a non-limiting example, a salt derivative can be prepared by contacting a free base with a sufficient amount of the desired acid to produce a salt. A free base may be regenerated by treating the salt with a suitable dilute aqueous base solution such as dilute aqueous sodium hydroxide (NaOH), potassium carbonate, ammonia, and sodium bicarbonate. As an example, in many cases, a pesticide, such as 2,4-D, is made more water-soluble by converting it to its dimethylamine salt.

Molecules of Formula One may be formulated into stable complexes with a solvent, such that the complex remains intact after the non-complexed solvent is removed. These complexes are often referred to as “solvates.” However, it is particularly desirable to form stable hydrates with water as the solvent.

Molecules of Formula One may be made into ester derivatives. These ester derivatives can then be applied in the same manner as the invention disclosed in this document is applied.

Molecules of Formula One may be made as various crystal polymorphs. Polymorphism is important in the development of agrochemicals since different crystal polymorphs or structures of the same molecule can have vastly different physical properties and biological performances.

Molecules of Formula One may be made with different isotopes. Of particular importance are molecules having ²H (also known as deuterium) in place of ¹H.

Molecules of Formula One may be made with different radionuclides. Of particular importance are molecules having ¹⁴C.

Stereoisomers

Molecules of Formula One may exist as one or more stereoisomers. Thus, certain molecules can be produced as racemic mixtures. It will be appreciated by those skilled in the art that one stereoisomer may be more active than the other stereoisomers. Individual stereoisomers may be obtained by known selective synthetic procedures, by conventional synthetic procedures using resolved starting materials, or by conventional resolution procedures. Certain molecules disclosed in this document can exist as two or more isomers. The various isomers include geometric isomers, diastereomers, and enantiomers. Thus, the molecules disclosed in this document include geometric isomers, racemic mixtures, individual stereoisomers, and optically active mixtures. It will be appreciated by those skilled in the art that one isomer may be more active than the others. The structures disclosed in the present disclosure are drawn in only one geometric form for clarity, but are intended to represent all geometric forms of the molecule.

Combinations

Molecules of Formula One may also be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with one or more compounds having acaricidal, algicidal, avicidal, bactericidal, fungicidal, herbicidal, insecticidal, molluscicidal, nematicidal, rodenticidal, or virucidal properties. Additionally, the molecules of Formula One may also be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with compounds that are antifeedants, bird repellents, chemosterilants, herbicide safeners, insect attractants, insect repellents, mammal repellents, mating disrupters, plant activators, plant growth regulators, or synergists. Examples of such compounds in the above groups that may be used with the Molecules of Formula One are -(3-ethoxypropyl)mercury bromide, 1,2-dichloropropane, 1,3-dichloropropene, 1-methylcyclopropene, 1-naphthol, 2-(octylthio)ethanol, 2,3,5-tri-iodobenzoic acid, 2,3,6-TBA, 2,3,6-TBA-dimethylammonium, 2,3,6-TBA-lithium, 2,3,6-TBA-potassium, 2,3,6-TBA-sodium, 2,4,5-T, 2,4,5-T-2-butoxypropyl, 2,4,5-T-2-ethylhexyl, 2,4,5-T-3-butoxypropyl, 2,4,5-TB, 2,4,5-T-butometyl, 2,4,5-T-butotyl, 2,4,5-T-butyl, 2,4,5-T-isobutyl, 2,4,5-T-isoctyl, 2,4,5-T-isopropyl, 2,4,5-T-methyl, 2,4,5-T-pentyl, 2,4,5-T-sodium, 2,4,5-T-triethylammonium, 2,4,5-T-trolamine, 2,4-D, 2,4-D-2-butoxypropyl, 2,4-D-2-ethylhexyl, 2,4-D-3-butoxypropyl, 2,4-D-ammonium, 2,4-DB, 2,4-DB-butyl, 2,4-DB-dimethylammonium, 2,4-DB-isoctyl, 2,4-DB-potassium, 2,4-DB-sodium, 2,4-D-butotyl, 2,4-D-butyl, 2,4-D-diethylammonium, 2,4-D-dimethylammonium, 2,4-D-diolamine, 2,4-D-dodecylammonium, 2,4-DEB, 2,4-DEP, 2,4-D-ethyl, 2,4-D-heptylammonium, 2,4-D-isobutyl, 2,4-D-isoctyl, 2,4-D-isopropyl, 2,4-D-isopropylammonium, 2,4-D-lithium, 2,4-D-meptyl, 2,4-D-methyl, 2,4-D-octyl, 2,4-D-pentyl, 2,4-D-potassium, 2,4-D-propyl, 2,4-D-sodium, 2,4-D-tefuryl, 2,4-D-tetradecylammonium, 2,4-D-triethylammonium, 2,4-D-tris(2-hydroxypropyl)ammonium, 2,4-D-trolamine, 2iP, 2-methoxyethylmercury chloride, 2-phenylphenol, 3,4-DA, 3,4-DB, 3,4-DP, 4-aminopyridine, 4-CPA, 4-CPA-potassium, 4-CPA-sodium, 4-CPB, 4-CPP, 4-hydroxyphenethyl alcohol, 8-hydroxyquinoline sulfate, 8-phenylmercurioxyquinoline, abamectin, abscisic acid, ACC, acephate, acequinocyl, acetamiprid, acethion, acetochlor, acetophos, acetoprole, acibenzolar, acibenzolar-S-methyl, acifluorfen, acifluorfen-methyl, acifluorfen-sodium, aclonifen, acrep, acrinathrin, acrolein, acrylonitrile, acypetacs, acypetacs-copper, acypetacs-zinc, alachlor, alanycarb, albendazole, aldicarb, aldimorph, aldoxycarb, aldrin, allethrin, allicin, allidochlor, allosamidin, alloxydim, alloxydim-sodium, allyl alcohol, allyxycarb, alorac, alpha-cypermethrin, alpha-endosulfan, ametoctradin, ametridione, ametryn, amibuzin, amicarbazone, amicarthiazol, amidithion, amidoflumet, amidosulfuron, aminocarb, aminocyclopyrachlor, aminocyclopyrachlor-methyl, aminocyclopyrachlor-potassium, aminopyralid, aminopyralid-potassium, aminopyralid-tris(2-hydroxypropyl)ammonium, amiprofos-methyl, amiprophos, amisulbrom, amiton, amiton oxalate, amitraz, amitrole, ammonium sulfamate, ammonium α-naphthaleneacetate, amobam, ampropylfos, anabasine, ancymidol, anilazine, anilofos, anisuron, anthraquinone, antu, apholate, aramite, arsenous oxide, asomate, aspirin, asulam, asulam-potassium, asulam-sodium, athidathion, atraton, atrazine, aureofungin, aviglycine, aviglycine hydrochloride, azaconazole, azadirachtin, azafenidin, azamethiphos, azimsulfuron, azinphos-ethyl, azinphos-methyl, aziprotryne, azithiram, azobenzene, azocyclotin, azothoate, azoxystrobin, bachmedesh, barban, barium hexafluorosilicate, barium polysulfide, barthrin, BCPC, beflubutamid, benalaxyl, benalaxyl-M, benazolin, benazolin-dimethylammonium, benazolin-ethyl, benazolin-potassium, bencarbazone, benclothiaz, bendiocarb, benfluralin, benfuracarb, benfuresate, benodanil, benomyl, benoxacor, benoxafos, benquinox, bensulfuron, bensulfuron-methyl, bensulide, bensultap, bentaluron, bentazone, bentazone-sodium, benthiavalicarb, benthiavalicarb-isopropyl, benthiazole, bentranil, benzadox, benzadox-ammonium, benzalkonium chloride, benzamacril, benzamacril-isobutyl, benzamorf, benzfendizone, benzipram, benzobicyclon, benzofenap, benzofluor, benzohydroxamic acid, benzoximate, benzoylprop, benzoylprop-ethyl, benzthiazuron, benzyl benzoate, benzyladenine, berberine, berberine chloride, beta-cyfluthrin, beta-cypermethrin, bethoxazin, bicyclopyrone, bifenazate, bifenox, bifenthrin, bifujunzhi, bilanafos, bilanafos-sodium, binapacryl, bingqingxiao, bioallethrin, bioethanomethrin, biopermethrin, bioresmethrin, biphenyl, bisazir, bismerthiazol, bispyribac, bispyribac-sodium, bistrifluron, bitertanol, bithionol, bixafen, blasticidin-S, borax, Bordeaux mixture, boric acid, boscalid, brassinolide, brassinolide-ethyl, brevicomin, brodifacoum, brofenvalerate, brofluthrinate, bromacil, bromacil-lithium, bromacil-sodium, bromadiolone, bromethalin, bromethrin, bromfenvinfos, bromoacetamide, bromobonil, bromobutide, bromocyclen, bromo-DDT, bromofenoxim, bromophos, bromophos-ethyl, bromopropylate, bromothalonil, bromoxynil, bromoxynil butyrate, bromoxynil heptanoate, bromoxynil octanoate, bromoxynil-potassium, brompyrazon, bromuconazole, bronopol, bucarpolate, bufencarb, buminafos, bupirimate, buprofezin, Burgundy mixture, busulfan, butacarb, butachlor, butafenacil, butamifos, butathiofos, butenachlor, butethrin, buthidazole, buthiobate, buthiuron, butocarboxim, butonate, butopyronoxyl, butoxycarboxim, butralin, butroxydim, buturon, butylamine, butylate, cacodylic acid, cadusafos, cafenstrole, calcium arsenate, calcium chlorate, calcium cyanamide, calcium polysulfide, calvinphos, cambendichlor, camphechlor, camphor, captafol, captan, carbamorph, carbanolate, carbaryl, carbasulam, carbendazim, carbendazim benzenesulfonate, carbendazim sulfite, carbetamide, carbofuran, carbon disulfide, carbon tetrachloride, carbophenothion, carbosulfan, carboxazole, carboxide, carboxin, carfentrazone, carfentrazone-ethyl, carpropamid, cartap, cartap hydrochloride, carvacrol, carvone, CDEA, cellocidin, CEPC, ceralure, Cheshunt mixture, chinomethionat, chitosan, chlobenthiazone, chlomethoxyfen, chloralose, chloramben, chloramben-ammonium, chloramben-diolamine, chloramben-methyl, chloramben-methylammonium, chloramben-sodium, chloramine phosphorus, chloramphenicol, chloraniformethan, chloranil, chloranocryl, chlorantraniliprole, chlorazifop, chlorazifop-propargyl, chlorazine, chlorbenside, chlorbenzuron, chlorbicyclen, chlorbromuron, chlorbufam, chlordane, chlordecone, chlordimeform, chlordimeform hydrochloride, chlorempenthrin, chlorethoxyfos, chloreturon, chlorfenac, chlorfenac-ammonium, chlorfenac-sodium, chlorfenapyr, chlorfenazole, chlorfenethol, chlorfenprop, chlorfenson, chlorfensulphide, chlorfenvinphos, chlorfluazuron, chlorflurazole, chlorfluren, chlorfluren-methyl, chlorflurenol, chlorflurenol-methyl, chloridazon, chlorimuron, chlorimuron-ethyl, chlormephos, chlormequat, chlormequat chloride, chlomidine, chlornitrofen, chlorobenzilate, chlorodinitronaphthalenes, chloroform, chloromebuform, chloromethiuron, chloroneb, chlorophacinone, chlorophacinone-sodium, chloropicrin, chloropon, chloropropylate, chlorothalonil, chlorotoluron, chloroxuron, chloroxynil, chlorphonium, chlorphonium chloride, chlorphoxim, chlorprazophos, chlorprocarb, chlorpropham, chlorpyrifos, chlorpyrifos-methyl, chlorquinox, chlorsulfuron, chlorthal, chlorthal-dimethyl, chlorthal-monomethyl, chlorthiamid, chlorthiophos, chlozolinate, choline chloride, chromafenozide, cinerin I, cinerin II, cinerins, cinidon-ethyl, cinmethylin, cinosulfuron, ciobutide, cisanilide, cismethrin, clethodim, climbazole, cliodinate, clodinafop, clodinafop-propargyl, cloethocarb, clofencet, clofencet-potassium, clofentezine, clofibric acid, clofop, clofop-isobutyl, clomazone, clomeprop, cloprop, cloproxydim, clopyralid, clopyralid-methyl, clopyralid-olamine, clopyralid-potassium, clopyralid-tris(2-hydroxypropyl)ammonium, cloquintocet, cloquintocet-mexyl, cloransulam, cloransulam-methyl, closantel, clothianidin, clotrimazole, cloxyfonac, cloxyfonac-sodium, CMA, codlelure, colophonate, copper acetate, copper acetoarsenite, copper arsenate, copper carbonate, basic, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper silicate, copper sulfate, copper zinc chromate, coumachlor, coumafuryl, coumaphos, coumatetralyl, coumithoate, coumoxystrobin, CPMC, CPMF, CPPC, credazine, cresol, crimidine, crotamiton, crotoxyphos, crufomate, cryolite, cue-lure, cufraneb, cumyluron, cuprobam, cuprous oxide, curcumenol, cyanamide, cyanatryn, cyanazine, cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyazofamid, cybutryne, cyclafuramid, cyclanilide, cyclethrin, cycloate, cycloheximide, cycloprate, cycloprothrin, cyclosulfamuron, cycloxaprid, cycloxydim, cycluron, cyenopyrafen, cyflufenamid, cyflumetofen, cyfluthrin, cyhalofop, cyhalofop-butyl, cyhalothrin, cyhexatin, cymiazole, cymiazole hydrochloride, cymoxanil, cyometrinil, cypendazole, cypermethrin, cyperquat, cyperquat chloride, cyphenothrin, cyprazine, cyprazole, cyproconazole, cyprodinil, cyprofuram, cypromid, cyprosulfamide, cyromazine, cythioate, daimuron, dalapon, dalapon-calcium, dalapon-magnesium, dalapon-sodium, daminozide, dayoutong, dazomet, dazomet-sodium, DBCP, d-camphor, DCIP, DCPTA, DDT, debacarb, decafentin, decarbofuran, dehydroacetic acid, delachlor, deltamethrin, demephion, demephion-O, demephion-S, demeton, demeton-methyl, demeton-O, demeton-O-methyl, demeton-S, demeton-S-methyl, demeton-S-methylsulphon, desmedipham, desmetryn, d-fanshiluquebingjuzhi, diafenthiuron, dialifos, di-allate, diamidafos, diatomaceous earth, diazinon, dibutyl phthalate, dibutyl succinate, dicamba, dicamba-diglycolamine, dicamba-dimethylammonium, dicamba-diolamine, dicamba-isopropylammonium, dicamba-methyl, dicamba-olamine, dicamba-potassium, dicamba-sodium, dicamba-trolamine, dicapthon, dichlobenil, dichlofenthion, dichlofluanid, dichlone, dichloralurea, dichlorbenzuron, dichlorflurenol, dichlorflurenol-methyl, dichlormate, dichlormid, dichlorophen, dichlorprop, dichlorprop-2-ethylhexyl, dichlorprop-butotyl, dichlorprop-dimethylammonium, dichlorprop-ethylammonium, dichlorprop-isoctyl, dichlorprop-methyl, dichlorprop-P, dichlorprop-P-2-ethylhexyl, dichlorprop-P-dimethylammonium, dichlorprop-potassium, dichlorprop-sodium, dichlorvos, dichlozoline, diclobutrazol, diclocymet, diclofop, diclofop-methyl, diclomezine, diclomezine-sodium, dicloran, diclosulam, dicofol, dicoumarol, dicresyl, dicrotophos, dicyclanil, dicyclonon, dieldrin, dienochlor, diethamquat, diethamquat dichloride, diethatyl, diethatyl-ethyl, diethofencarb, dietholate, diethyl pyrocarbonate, diethyltoluamide, difenacoum, difenoconazole, difenopenten, difenopenten-ethyl, difenoxuron, difenzoquat, difenzoquat metilsulfate, difethialone, diflovidazin, diflubenzuron, diflufenican, diflufenzopyr, diflufenzopyr-sodium, diflumetorim, dikegulac, dikegulac-sodium, dilor, dimatif, dimefluthrin, dimefox, dimefuron, dimepiperate, dimetachlone, dimetan, dimethacarb, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimethipin, dimethirimol, dimethoate, dimethomorph, dimethrin, dimethyl carbate, dimethyl phthalate, dimethylvinphos, dimetilan, dimexano, dimidazon, dimoxystrobin, dinex, dinex-diclexine, dingjunezuo, diniconazole, diniconazole-M, dinitramine, dinobuton, dinocap, dinocap-4, dinocap-6, dinocton, dinofenate, dinopenton, dinoprop, dinosam, dinoseb, dinoseb acetate, dinoseb-ammonium, dinoseb-diolamine, dinoseb-sodium, dinoseb-trolamine, dinosulfon, dinotefuran, dinoterb, dinoterb acetate, dinoterbon, diofenolan, dioxabenzofos, dioxacarb, dioxathion, diphacinone, diphacinone-sodium, diphenamid, diphenyl sulfone, diphenylamine, dipropalin, dipropetryn, dipyrithione, diquat, diquat dibromide, disparlure, disul, disulfiram, disulfoton, disul-sodium, ditalimfos, dithianon, dithicrofos, dithioether, dithiopyr, diuron, d-limonene, DMPA, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium, dodemorph, dodemorph acetate, dodemorph benzoate, dodicin, dodicin hydrochloride, dodicin-sodium, dodine, dofenapyn, dominicalure, doramectin, drazoxolon, DSMA, dufulin, EBEP, EBP, ecdysterone, edifenphos, eglinazine, eglinazine-ethyl, emamectin, emamectin benzoate, EMPC, empenthrin, endosulfan, endothal, endothal-diammonium, endothal-dipotassium, endothal-disodium, endothion, endrin, enestroburin, EPN, epocholeone, epofenonane, epoxiconazole, eprinomectin, epronaz, EPTC, erbon, ergocalciferol, erlujixiancaoan, esdépalléthrine, esfenvalerate, esprocarb, etacelasil, etaconazole, etaphos, etem, ethaboxam, ethachlor, ethalfluralin, ethametsulfuron, ethametsulfuron-methyl, ethaprochlor, ethephon, ethidimuron, ethiofencarb, ethiolate, ethion, ethiozin, ethiprole, ethirimol, ethoate-methyl, ethofumesate, ethohexadiol, ethoprophos, ethoxyfen, ethoxyfen-ethyl, ethoxyquin, ethoxysulfuron, ethychlozate, ethyl formate, ethyl α-naphthaleneacetate, ethyl-DDD, ethylene, ethylene dibromide, ethylene dichloride, ethylene oxide, ethylicin, ethylmercury 2,3-dihydroxypropyl mercaptide, ethylmercury acetate, ethylmercury bromide, ethylmercury chloride, ethylmercury phosphate, etinofen, etnipromid, etobenzanid, etofenprox, etoxazole, etridiazole, etrimfos, eugenol, EXD, famoxadone, famphur, fenamidone, fenaminosulf, fenamiphos, fenapanil, fenarimol, fenasulam, fenazaflor, fenazaquin, fenbuconazole, fenbutatin oxide, fenchlorazole, fenchlorazole-ethyl, fenchlorphos, fenclorim, fenethacarb, fenfluthrin, fenfuram, fenhexamid, fenitropan, fenitrothion, fenjuntong, fenobucarb, fenoprop, fenoprop-3-butoxypropyl, fenoprop-butometyl, fenoprop-butotyl, fenoprop-butyl, fenoprop-isoctyl, fenoprop-methyl, fenoprop-potassium, fenothiocarb, fenoxacrim, fenoxanil, fenoxaprop, fenoxaprop-ethyl, fenoxaprop-P, fenoxaprop-P-ethyl, fenoxasulfone, fenoxycarb, fenpiclonil, fenpirithrin, fenpropathrin, fenpropidin, fenpropimorph, fenpyrazamine, fenpyroximate, fenridazon, fenridazon-potassium, fenridazon-propyl, fenson, fensulfothion, fenteracol, fenthiaprop, fenthiaprop-ethyl, fenthion, fenthion-ethyl, fentin, fentin acetate, fentin chloride, fentin hydroxide, fentrazamide, fentrifanil, fenuron, fenuron TCA, fenvalerate, ferbam, ferimzone, ferrous sulfate, fipronil, flamprop, flamprop-isopropyl, flamprop-M, flamprop-methyl, flamprop-M-isopropyl, flamprop-M-methyl, flazasulfuron, flocoumafen, flometoquin, flonicamid, florasulam, fluacrypyrim, fluazifop, fluazifop-butyl, fluazifop-methyl, fluazifop-P, fluazifop-P-butyl, fluazinam, fluazolate, fluazuron, flubendiamide, flubenzimine, flucarbazone, flucarbazone-sodium, flucetosulfuron, fluchloralin, flucofuron, flucycloxuron, flucythrinate, fludioxonil, fluenetil, fluensulfone, flufenacet, flufenerim, flufenican, flufenoxuron, flufenprox, flufenpyr, flufenpyr-ethyl, flufiprole, flumethrin, flumetover, flumetralin, flumetsulam, flumezin, flumiclorac, flumiclorac-pentyl, flumioxazin, flumipropyn, flumorph, fluometuron, fluopicolide, fluopyram, fluorbenside, fluoridamid, fluoroacetamide, fluorodifen, fluoroglycofen, fluoroglycofen-ethyl, fluoroimide, fluoromidine, fluoronitrofen, fluothiuron, fluotrimazole, fluoxastrobin, flupoxam, flupropacil, flupropadine, flupropanate, flupropanate-sodium, flupyradifurone, flupyrsulfuron, flupyrsulfuron-methyl, flupyrsulfuron-methyl-sodium, fluquinconazole, flurazole, flurenol, flurenol-butyl, flurenol-methyl, fluridone, flurochloridone, fluroxypyr, fluroxypyr-butometyl, fluroxypyr-meptyl, flurprimidol, flursulamid, flurtamone, flusilazole, flusulfamide, fluthiacet, fluthiacet-methyl, flutianil, flutolanil, flutriafol, fluvalinate, fluxapyroxad, fluxofenim, folpet, fomesafen, fomesafen-sodium, fonofos, foramsulfuron, forchlorfenuron, formaldehyde, formetanate, formetanate hydrochloride, formothion, formparanate, formparanate hydrochloride, fosamine, fosamine-ammonium, fosetyl, fosetyl-aluminium, fosmethilan, fospirate, fosthiazate, fosthietan, frontalin, fuberidazole, fucaojing, fucaomi, funaihecaoling, fuphenthiourea, furalane, furalaxyl, furamethrin, furametpyr, furathiocarb, furcarbanil, furconazole, furconazole-cis, furethrin, furfural, furilazole, furmecyclox, furophanate, furyloxyfen, gamma-cyhalothrin, gamma-HCH, genit, gibberellic acid, gibberellins, gliftor, glufosinate, glufosinate-ammonium, glufosinate-P, glufosinate-P-ammonium, glufosinate-P-sodium, glyodin, glyoxime, glyphosate, glyphosate-diammonium, glyphosate-dimethylammonium, glyphosate-isopropylammonium, glyphosate-monoammonium, glyphosate-potassium, glyphosate-sesquisodium, glyphosate-trimesium, glyphosine, gossyplure, grandlure, griseofulvin, guazatine, guazatine acetates, halacrinate, halfenprox, halofenozide, halosafen, halosulfuron, halosulfuron-methyl, haloxydine, haloxyfop, haloxyfop-etotyl, haloxyfop-methyl, haloxyfop-P, haloxyfop-P-etotyl, haloxyfop-P-methyl, haloxyfop-sodium, HCH, hemel, hempa, HEOD, heptachlor, heptenophos, heptopargil, heterophos, hexachloroacetone, hexachlorobenzene, hexachlorobutadiene, hexachlorophene, hexaconazole, hexaflumuron, hexaflurate, hexalure, hexamide, hexazinone, hexylthiofos, hexythiazox, HHDN, holosulf, huancaiwo, huangcaoling, huanjunzuo, hydramethylnon, hydrargaphen, hydrated lime, hydrogen cyanide, hydroprene, hymexazol, hyquincarb, IAA, IBA, icaridin, imazalil, imazalil nitrate, imazalil sulfate, imazamethabenz, imazamethabenz-methyl, imazamox, imazamox-ammonium, imazapic, imazapic-ammonium, imazapyr, imazapyr-isopropylammonium, imazaquin, imazaquin-ammonium, imazaquin-methyl, imazaquin-sodium, imazethapyr, imazethapyr-ammonium, imazosulfuron, imibenconazole, imicyafos, imidacloprid, imidaclothiz, iminoctadine, iminoctadine triacetate, iminoctadine trialbesilate, imiprothrin, inabenfide, indanofan, indaziflam, indoxacarb, inezin, iodobonil, iodocarb, iodomethane, iodosulfuron, iodosulfuron-methyl, iodosulfuron-methyl-sodium, iofensulfuron, iofensulfuron-sodium, ioxynil, ioxynil octanoate, ioxynil-lithium, ioxynil-sodium, ipazine, ipconazole, ipfencarbazone, iprobenfos, iprodione, iprovalicarb, iprymidam, ipsdienol, ipsenol, IPSP, isamidofos, isazofos, isobenzan, isocarbamid, isocarbophos, isocil, isodrin, isofenphos, isofenphos-methyl, isolan, isomethiozin, isonoruron, isopolinate, isoprocarb, isopropalin, isoprothiolane, isoproturon, isopyrazam, isopyrimol, isothioate, isotianil, isouron, isovaledione, isoxaben, isoxachlortole, isoxadifen, isoxadifen-ethyl, isoxaflutole, isoxapyrifop, isoxathion, ivermectin, izopamfos, japonilure, japothrins, jasmolin I, jasmolin II, jasmonic acid, jiahuangchongzong, jiajizengxiaolin, jiaxiangjunzhi, jiecaowan, jiecaoxi, jodfenphos, juvenile hormone I, juvenile hormone II, juvenile hormone III, kadethrin, karbutilate, karetazan, karetazan-potassium, kasugamycin, kasugamycin hydrochloride, kejunlin, kelevan, ketospiradox, ketospiradox-potassium, kinetin, kinoprene, kresoxim-methyl, kuicaoxi, lactofen, lambda-cyhalothrin, latilure, lead arsenate, lenacil, lepimectin, leptophos, lindane, lineatin, linuron, lirimfos, litlure, looplure, lufenuron, lvdingjunzhi, lvxiancaolin, lythidathion, MAA, malathion, maleic hydrazide, malonoben, maltodextrin, MAMA, mancopper, mancozeb, mandipropamid, maneb, matrine, mazidox, MCPA, MCPA-2-ethylhexyl, MCPA-butotyl, MCPA-butyl, MCPA-dimethylammonium, MCPA-diolamine, MCPA-ethyl, MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl, MCPA-methyl, MCPA-olamine, MCPA-potassium, MCPA-sodium, MCPA-thioethyl, MCPA-trolamine, MCPB, MCPB-ethyl, MCPB-methyl, MCPB-sodium, mebenil, mecarbam, mecarbinzid, mecarphon, mecoprop, mecoprop-2-ethylhexyl, mecoprop-dimethylammonium, mecoprop-diolamine, mecoprop-ethadyl, mecoprop-isoctyl, mecoprop-methyl, mecoprop-P, mecoprop-P-2-ethylhexyl, mecoprop-P-dimethylammonium, mecoprop-P-isobutyl, mecoprop-potassium, mecoprop-P-potassium, mecoprop-sodium, mecoprop-trolamine, medimeform, medinoterb, medinoterb acetate, medlure, mefenacet, mefenpyr, mefenpyr-diethyl, mefluidide, mefluidide-diolamine, mefluidide-potassium, megatomoic acid, menazon, mepanipyrim, meperfluthrin, mephenate, mephosfolan, mepiquat, mepiquat chloride, mepiquat pentaborate, mepronil, meptyldinocap, mercuric chloride, mercuric oxide, mercurous chloride, merphos, mesoprazine, mesosulfuron, mesosulfuron-methyl, mesotrione, mesulfen, mesulfenfos, metaflumizone, metalaxyl, metalaxyl-M, metaldehyde, metam, metam-ammonium, metamifop, metamitron, metam-potassium, metam-sodium, metazachlor, metazosulfuron, metazoxolon, metconazole, metepa, metflurazon, methabenzthiazuron, methacrifos, methalpropalin, methamidophos, methasulfocarb, methazole, methfuroxam, methidathion, methiobencarb, methiocarb, methiopyrisulfuron, methiotepa, methiozolin, methiuron, methocrotophos, methometon, methomyl, methoprene, methoprotryne, methoquin-butyl, methothrin, methoxychlor, methoxyfenozide, methoxyphenone, methyl apholate, methyl bromide, methyl eugenol, methyl iodide, methyl isothiocyanate, methylacetophos, methylchloroform, methyldymron, methylene chloride, methylmercury benzoate, methylmercury dicyandiamide, methylmercury pentachlorophenoxide, methylneodecanamide, metiram, metobenzuron, metobromuron, metofluthrin, metolachlor, metolcarb, metominostrobin, metosulam, metoxadiazone, metoxuron, metrafenone, metribuzin, metsulfovax, metsulfuron, metsulfuron-methyl, mevinphos, mexacarbate, mieshuan, milbemectin, milbemycin oxime, milneb, mipafox, mirex, MNAF, moguchun, molinate, molosultap, monalide, monisouron, monochloroacetic acid, monocrotophos, monolinuron, monosulfuron, monosulfuron-ester, monuron, monuron TCA, morfamquat, morfamquat dichloride, moroxydine, moroxydine hydrochloride, morphothion, morzid, moxidectin, MSMA, muscalure, myclobutanil, myclozolin, N-(ethylmercury)-p-toluenesulphonanilide, nabam, naftalofos, naled, naphthalene, naphthaleneacetamide, naphthalic anhydride, naphthoxyacetic acids, naproanilide, napropamide, naptalam, naptalam-sodium, natamycin, neburon, niclosamide, niclosamide-olamine, nicosulfuron, nicotine, nifluridide, nipyraclofen, nitenpyram, nithiazine, nitralin, nitrapyrin, nitrilacarb, nitrofen, nitrofluorfen, nitrostyrene, nitrothal-isopropyl, norbormide, norflurazon, nomicotine, noruron, novaluron, noviflumuron, nuarimol, OCH, octachlorodipropyl ether, octhilinone, ofurace, omethoate, orbencarb, orfralure, ortho-dichlorobenzene, orthosulfamuron, oryctalure, orysastrobin, oryzalin, osthol, ostramone, oxabetrinil, oxadiargyl, oxadiazon, oxadixyl, oxamate, oxamyl, oxapyrazon, oxapyrazon-dimolamine, oxapyrazon-sodium, oxasulfuron, oxaziclomefone, oxine-copper, oxolinic acid, oxpoconazole, oxpoconazole fumarate, oxycarboxin, oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyfluorfen, oxymatrine, oxytetracycline, oxytetracycline hydrochloride, paclobutrazol, paichongding, para-dichlorobenzene, parafluron, paraquat, paraquat dichloride, paraquat dimetilsulfate, parathion, parathion-methyl, parinol, pebulate, pefurazoate, pelargonic acid, penconazole, pencycuron, pendimethalin, penflufen, penfluron, penoxsulam, pentachlorophenol, pentanochlor, penthiopyrad, pentmethrin, pentoxazone, perfluidone, permethrin, pethoxamid, phenamacril, phenazine oxide, phenisopham, phenkapton, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenothrin, phenproxide, phenthoate, phenylmercuriurea, phenylmercury acetate, phenylmercury chloride, phenylmercury derivative of pyrocatechol, phenylmercury nitrate, phenylmercury salicylate, phorate, phosacetim, phosalone, phosdiphen, phosfolan, phosfolan-methyl, phosglycin, phosmet, phosnichlor, phosphamidon, phosphine, phosphocarb, phosphorus, phostin, phoxim, phoxim-methyl, phthalide, picloram, picloram-2-ethylhexyl, picloram-isoctyl, picloram-methyl, picloram-olamine, picloram-potassium, picloram-triethylammonium, picloram-tris(2-hydroxypropyl)ammonium, picolinafen, picoxystrobin, pindone, pindone-sodium, pinoxaden, piperalin, piperonyl butoxide, piperonyl cyclonene, piperophos, piproctanyl, piproctanyl bromide, piprotal, pirimetaphos, pirimicarb, pirimioxyphos, pirimiphos-ethyl, pirimiphos-methyl, plifenate, polycarbamate, polyoxins, polyoxorim, polyoxorim-zinc, polythialan, potassium arsenite, potassium azide, potassium cyanate, potassium gibberellate, potassium naphthenate, potassium polysulfide, potassium thiocyanate, potassium α-naphthaleneacetate, pp′-DDT, prallethrin, precocene I, precocene II, precocene III, pretilachlor, primidophos, primisulfuron, primisulfuron-methyl, probenazole, prochloraz, prochloraz-manganese, proclonol, procyazine, procymidone, prodiamine, profenofos, profluazol, profluralin, profluthrin, profoxydim, proglinazine, proglinazine-ethyl, prohexadione, prohexadione-calcium, prohydrojasmon, promacyl, promecarb, prometon, prometryn, promurit, propachlor, propamidine, propamidine dihydrochloride, propamocarb, propamocarb hydrochloride, propanil, propaphos, propaquizafop, propargite, proparthrin, propazine, propetamphos, propham, propiconazole, propineb, propisochlor, propoxur, propoxycarbazone, propoxycarbazone-sodium, propyl isome, propyrisulfuron, propyzamide, proquinazid, prosuler, prosulfalin, prosulfocarb, prosulfuron, prothidathion, prothiocarb, prothiocarb hydrochloride, prothioconazole, prothiofos, prothoate, protrifenbute, proxan, proxan-sodium, prynachlor, pydanon, pymetrozine, pyracarbolid, pyraclofos, pyraclonil, pyraclostrobin, pyraflufen, pyraflufen-ethyl, pyrafluprole, pyramat, pyrametostrobin, pyraoxystrobin, pyrasulfotole, pyrazolynate, pyrazophos, pyrazosulfuron, pyrazosulfuron-ethyl, pyrazothion, pyrazoxyfen, pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyribambenz-isopropyl, pyribambenz-propyl, pyribencarb, pyribenzoxim, pyributicarb, pyriclor, pyridaben, pyridafol, pyridalyl, pyridaphenthion, pyridate, pyridinitril, pyrifenox, pyrifluquinazon, pyriftalid, pyrimethanil, pyrimidifen, pyriminobac, pyriminobac-methyl, pyrimisulfan, pyrimitate, pyrinuron, pyriofenone, pyriprole, pyripropanol, pyriproxyfen, pyrithiobac, pyrithiobac-sodium, pyrolan, pyroquilon, pyroxasulfone, pyroxsulam, pyroxychlor, pyroxyfur, quassia, quinacetol, quinacetol sulfate, quinalphos, quinalphos-methyl, quinazamid, quinclorac, quinconazole, quinmerac, quinoclamine, quinonamid, quinothion, quinoxyfen, quintiofos, quintozene, quizalofop, quizalofop-ethyl, quizalofop-P, quizalofop-P-ethyl, quizalofop-P-tefuryl, quwenzhi, quyingding, rabenzazole, rafoxanide, rebemide, resmethrin, rhodethanil, rhodojaponin-III, ribavirin, rimsulfuron, rotenone, ryania, saflufenacil, saijunmao, saisentong, salicylanilide, sanguinarine, santonin, schradan, scilliroside, sebuthylazine, secbumeton, sedaxane, selamectin, semiamitraz, semiamitraz chloride, sesamex, sesamolin, sethoxydim, shuangjiaancaolin, siduron, siglure, silafluofen, silatrane, silica gel, silthiofam, simazine, simeconazole, simeton, simetryn, sintofen, SMA, S-metolachlor, sodium arsenite, sodium azide, sodium chlorate, sodium fluoride, sodium fluoroacetate, sodium hexafluorosilicate, sodium naphthenate, sodium orthophenylphenoxide, sodium pentachlorophenoxide, sodium polysulfide, sodium thiocyanate, sodium α-naphthaleneacetate, sophamide, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, spiroxamine, streptomycin, streptomycin sesquisulfate, strychnine, sulcatol, sulcofuron, sulcofuron-sodium, sulcotrione, sulfallate, sulfentrazone, sulfiram, sulfluramid, sulfometuron, sulfometuron-methyl, sulfosulfuron, sulfotep, sulfoxaflor, sulfoxide, sulfoxime, sulfur, sulfuric acid, sulfuryl fluoride, sulglycapin, sulprofos, sultropen, swep, tau-fluvalinate, tavron, tazimcarb, TCA, TCA-ammonium, TCA-calcium, TCA-ethadyl, TCA-magnesium, TCA-sodium, TDE, tebuconazole, tebufenozide, tebufenpyrad, tebufloquin, tebupirimfos, tebutam, tebuthiuron, tecloftalam, tecnazene, tecoram, teflubenzuron, tefluthrin, tefuryltrione, tembotrione, temephos, tepa, TEPP, tepraloxydim, terallethrin, terbacil, terbucarb, terbuchlor, terbufos, terbumeton, terbuthylazine, terbutryn, tetcyclacis, tetrachloroethane, tetrachlorvinphos, tetraconazole, tetradifon, tetrafluron, tetramethrin, tetramethylfluthrin, tetramine, tetranactin, tetrasul, thallium sulfate, thenylchlor, theta-cypermethrin, thiabendazole, thiacloprid, thiadifluor, thiamethoxam, thiapronil, thiazafluron, thiazopyr, thicrofos, thicyofen, thidiazimin, thidiazuron, thiencarbazone, thiencarbazone-methyl, thifensulfuron, thifensulfuron-methyl, thifluzamide, thiobencarb, thiocarboxime, thiochlorfenphim, thiocyclam, thiocyclam hydrochloride, thiocyclam oxalate, thiodiazole-copper, thiodicarb, thiofanox, thiofluoximate, thiohempa, thiomersal, thiometon, thionazin, thiophanate, thiophanate-methyl, thioquinox, thiosemicarbazide, thiosultap, thiosultap-diammonium, thiosultap-disodium, thiosultap-monosodium, thiotepa, thiram, thuringiensin, tiadinil, tiaojiean, tiocarbazil, tioclorim, tioxymid, tirpate, tolclofos-methyl, tolfenpyrad, tolylfluanid, tolylmercury acetate, topramezone, tralkoxydim, tralocythrin, tralomethrin, tralopyril, transfluthrin, transpermethrin, tretamine, triacontanol, triadimefon, triadimenol, triafamone, tri-allate, triamiphos, triapenthenol, triarathene, triarimol, triasulfuron, triazamate, triazbutil, triaziflam, triazophos, triazoxide, tribenuron, tribenuron-methyl, tribufos, tributyltin oxide, tricamba, trichlamide, trichlorfon, trichlormetaphos-3, trichloronat, triclopyr, triclopyr-butotyl, triclopyr-ethyl, triclopyr-triethylammonium, tricyclazole, tridemorph, tridiphane, trietazine, trifenmorph, trifenofos, trifloxystrobin, trifloxysulfuron, trifloxysulfuron-sodium, triflumizole, triflumuron, trifluralin, triflusulfuron, triflusulfuron-methyl, trifop, trifop-methyl, trifopsime, triforine, trihydroxytriazine, trimedlure, trimethacarb, trimeturon, trinexapac, trinexapac-ethyl, triprene, tripropindan, triptolide, tritac, triticonazole, tritosulfuron, trunc-call, uniconazole, uniconazole-P, urbacide, uredepa, valerate, validamycin, valifenalate, valone, vamidothion, vangard, vaniliprole, vernolate, vinclozolin, warfarin, warfarin-potassium, warfarin-sodium, xiaochongliulin, xinjunan, xiwojunan, XMC, xylachlor, xylenols, xylylcarb, yishijing, zarilamid, zeatin, zengxiaoan, zeta-cypermethrin, zinc naphthenate, zinc phosphide, zinc thiazole, zineb, ziram, zolaprofos, zoxamide, zuomihuanglong, α-chlorohydrin, α-ecdysone, α-multistriatin, and α-naphthaleneacetic acid. For more information consult the “COMPENDIUM OF PESTICIDE COMMON NAMES” located at http://www.alanwood.net/pesticides/index.html. Also consult “THE PESTICIDE MANUAL” 14th Edition, edited by C D S Tomlin, copyright 2006 by British Crop Production Council, or its prior or more recent editions.

Biopesticides

Molecules of Formula One may also be used in combination (such as in a compositional mixture, or a simultaneous or sequential application) with one or more biopesticides. The term “biopesticide” is used for microbial biological pest control agents that are applied in a similar manner to chemical pesticides. Commonly these are bacterial, but there are also examples of fungal control agents, including Trichoderma spp. and Ampelomyces quisqualis (a control agent for grape powdery mildew). Bacillus subtilis are used to control plant pathogens. Weeds and rodents have also been controlled with microbial agents. One well-known insecticide example is Bacillus thuringiensis, a bacterial disease of Lepidoptera, Coleoptera, and Diptera. Because it has little effect on other organisms, it is considered more environmentally friendly than synthetic pesticides. Biological insecticides include products based on:

1. entomopathogenic fungi (e.g. Metarhizium anisopliae);

2. entomopathogenic nematodes (e.g. Steinemema feltiae); and

3. entomopathogenic viruses (e.g. Cydia pomonella granulovirus).

Other examples of entomopathogenic organisms include, but are not limited to, baculoviruses, bacteria and other prokaryotic organisms, fungi, protozoa and Microsproridia. Biologically derived insecticides include, but not limited to, rotenone, veratridine, as well as microbial toxins; insect tolerant or resistant plant varieties; and organisms modified by recombinant DNA technology to either produce insecticides or to convey an insect resistant property to the genetically modified organism. In one embodiment, the molecules of Formula One may be used with one or more biopesticides in the area of seed treatments and soil amendments. The Manual of Biocontrol Agents gives a review of the available biological insecticide (and other biology-based control) products. Copping L. G. (ed.) (2004). The Manual of Biocontrol Agents (formerly the Biopesticide Manual) 3rd Edition. British Crop Production Council (BCPC), Farnham, Surrey UK.

Other Active Compounds

Molecules of Formula One may also be used in combination (such as in a compositional mixture, or a simultaneous or sequential application) with one or more of the following:

-   1.     3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one; -   2.     3-(4′-chloro-2,4-dimethyl[1,1′-biphenyl]-3-yl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one; -   3. 4-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2(5H)-furanone; -   4.     4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-furanone; -   5.     3-chloro-N2-[(1S)-1-methyl-2-(methylsulfonyl)ethyl]-N1-[2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]-1,2-benzenedicarboxamide; -   6. 2-cyano-N-ethyl-4-fluoro-3-methoxy-benenesulfonamide; -   7. 2-cyano-N-ethyl-3-methoxy-benzenesulfonamide; -   8. 2-cyano-3-difluoromethoxy-N-ethyl-4-fluoro-benzenesulfonamide; -   9. 2-cyano-3-fluoromethoxy-N-ethyl-benzenesulfonamide; -   10. 2-cyano-6-fluoro-3-methoxy-N,N-dimethyl-benzenesulfonamide; -   11. 2-cyano-N-ethyl-6-fluoro-3-methoxy-N-methyl-benzenesulfonamide; -   12. 2-cyano-3-difluoromethoxy-N,N-dimethylbenzenesulfon-amide; -   13.     3-(difluoromethyl)-N-[2-(3,3-dimethylbutyl)phenyl]-1-methyl-1H-pyrazole-4-carboxamide; -   14.     N-ethyl-2,2-dimethylpropionamide-2-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)     hydrazone; -   15.     N-ethyl-2,2-dichloro-1-methylcyclopropane-carboxamide-2-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)     hydrazone nicotine; -   16.     O-{(E-)-[2-(4-chloro-phenyl)-2-cyano-1-(2-trifluoromethylphenyl)-vinyl]}     S-methyl thiocarbonate; -   17.     (E)-N1-[(2-chloro-1,3-thiazol-5-ylmethyl)]-N2-cyano-N1-methylacetamidine; -   18.     1-(6-chloropyridin-3-ylmethyl)-7-methyl-8-nitro-1,2,3,5,6,7-hexahydro-imidazo[1,2-a]pyridin-5-ol; -   19. 4-[4-chlorophenyl-(2-butylidine-hydrazono)methyl)]phenyl     mesylate; and -   20.     N-Ethyl-2,2-dichloro-1-methylcyclopropanecarboxamide-2-(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyl)hydrazone.     Synergistic Mixtures

Molecules of Formula One may be used with certain active compounds to form synergistic mixtures where the mode of action of such compounds compared to the mode of action of the molecules of Formula One are the same, similar, or different. Examples of modes of action include, but are not limited to: acetylcholinesterase inhibitor; sodium channel modulator; chitin biosynthesis inhibitor; GABA and glutamate-gated chloride channel antagonist; GABA and glutamate-gated chloride channel agonist; acetylcholine receptor agonist; acetylcholine receptor antagonist; MET I inhibitor; Mg-stimulated ATPase inhibitor; nicotinic acetylcholine receptor; Midgut membrane disrupter; oxidative phosphorylation disrupter, and ryanodine receptor (RyRs). Generally, weight ratios of the molecules of Formula One in a synergistic mixture with another compound are from about 10:1 to about 1:10, in another embodiment from about 5:1 to about 1:5, and in another embodiment from about 3:1, and in another embodiment about 1:1.

Formulations

A pesticide is rarely suitable for application in its pure form. It is usually necessary to add other substances so that the pesticide can be used at the required concentration and in an appropriate form, permitting ease of application, handling, transportation, storage, and maximum pesticide activity. Thus, pesticides are formulated into, for example, baits, concentrated emulsions, dusts, emulsifiable concentrates, fumigants, gels, granules, microencapsulations, seed treatments, suspension concentrates, suspoemulsions, tablets, water soluble liquids, water dispersible granules or dry flowables, wettable powders, and ultra-low volume solutions. For further information on formulation types see “Catalogue of Pesticide Formulation Types and International Coding System” Technical Monograph n° 2, 5th Edition by CropLife International (2002).

Pesticides are applied most often as aqueous suspensions or emulsions prepared from concentrated formulations of such pesticides. Such water-soluble, water-suspendable, or emulsifiable formulations are either solids, usually known as wettable powders, or water dispersible granules, or liquids usually known as emulsifiable concentrates, or aqueous suspensions. Wettable powders, which may be compacted to form water dispersible granules, comprise an intimate mixture of the pesticide, a carrier, and surfactants. The concentration of the pesticide is usually from about 10% to about 90% by weight. The carrier is usually selected from among the attapulgite clays, the montmorillonite clays, the diatomaceous earths, or the purified silicates. Effective surfactants, comprising from about 0.5% to about 10% of the wettable powder, are found among sulfonated lignins, condensed naphthalenesulfonates, naphthalenesulfonates, alkylbenzenesulfonates, alkyl sulfates, and non-ionic surfactants such as ethylene oxide adducts of alkyl phenols.

Emulsifiable concentrates of pesticides comprise a convenient concentration of a pesticide, such as from about 50 to about 500 grams per liter of liquid dissolved in a carrier that is either a water miscible solvent or a mixture of water-immiscible organic solvent and emulsifiers. Useful organic solvents include aromatics, especially xylenes and petroleum fractions, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, such as the terpenic solvents including rosin derivatives, aliphatic ketones such as cyclohexanone, and complex alcohols such as 2-ethoxyethanol. Suitable emulsifiers for emulsifiable concentrates are selected from conventional anionic and non-ionic surfactants.

Aqueous suspensions comprise suspensions of water-insoluble pesticides dispersed in an aqueous carrier at a concentration in the range from about 5% to about 50% by weight. Suspensions are prepared by finely grinding the pesticide and vigorously mixing it into a carrier comprised of water and surfactants. Ingredients, such as inorganic salts and synthetic or natural gums may also be added, to increase the density and viscosity of the aqueous carrier. It is often most effective to grind and mix the pesticide at the same time by preparing the aqueous mixture and homogenizing it in an implement such as a sand mill, ball mill, or piston-type homogenizer.

Pesticides may also be applied as granular compositions that are particularly useful for applications to the soil. Granular compositions usually contain from about 0.5% to about 10% by weight of the pesticide, dispersed in a carrier that comprises clay or a similar substance. Such compositions are usually prepared by dissolving the pesticide in a suitable solvent and applying it to a granular carrier which has been pre-formed to the appropriate particle size, in the range of from about 0.5 to about 3 mm Such compositions may also be formulated by making a dough or paste of the carrier and compound and crushing and drying to obtain the desired granular particle size.

Dusts containing a pesticide are prepared by intimately mixing the pesticide in powdered form with a suitable dusty agricultural carrier, such as kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1% to about 10% of the pesticide. They can be applied as a seed dressing or as a foliage application with a dust blower machine.

It is equally practical to apply a pesticide in the form of a solution in an appropriate organic solvent, usually petroleum oil, such as the spray oils, which are widely used in agricultural chemistry.

Pesticides can also be applied in the form of an aerosol composition. In such compositions the pesticide is dissolved or dispersed in a carrier, which is a pressure-generating propellant mixture. The aerosol composition is packaged in a container from which the mixture is dispensed through an atomizing valve.

Pesticide baits are formed when the pesticide is mixed with food or an attractant or both. When the pests eat the bait they also consume the pesticide. Baits may take the form of granules, gels, flowable powders, liquids, or solids. They can be used in pest harborages.

Fumigants are pesticides that have a relatively high vapor pressure and hence can exist as a gas in sufficient concentrations to kill pests in soil or enclosed spaces. The toxicity of the fumigant is proportional to its concentration and the exposure time. They are characterized by a good capacity for diffusion and act by penetrating the pest's respiratory system or being absorbed through the pest's cuticle. Fumigants are applied to control stored product pests under gas proof sheets, in gas sealed rooms or buildings or in special chambers.

Pesticides can be microencapsulated by suspending the pesticide particles or droplets in plastic polymers of various types. By altering the chemistry of the polymer or by changing factors in the processing, microcapsules can be formed of various sizes, solubility, wall thicknesses, and degrees of penetrability. These factors govern the speed with which the active ingredient within is released, which in turn, affects the residual performance, speed of action, and odor of the product.

Oil solution concentrates are made by dissolving pesticide in a solvent that will hold the pesticide in solution. Oil solutions of a pesticide usually provide faster knockdown and kill of pests than other formulations due to the solvents themselves having pesticidal action and the dissolution of the waxy covering of the integument increasing the speed of uptake of the pesticide. Other advantages of oil solutions include better storage stability, better penetration of crevices, and better adhesion to greasy surfaces.

Another embodiment is an oil-in-water emulsion, wherein the emulsion comprises oily globules which are each provided with a lamellar liquid crystal coating and are dispersed in an aqueous phase, wherein each oily globule comprises at least one compound which is agriculturally active, and is individually coated with a monolamellar or oligolamellar layer comprising: (1) at least one non-ionic lipophilic surface-active agent, (2) at least one non-ionic hydrophilic surface-active agent and (3) at least one ionic surface-active agent, wherein the globules having a mean particle diameter of less than 800 nanometers. Further information on the embodiment is disclosed in U.S. patent publication 20070027034 published Feb. 1, 2007, having patent application Ser. No. 11/495,228. For ease of use, this embodiment will be referred to as “OIWE”.

For further information consult “Insect Pest Management” 2nd Edition by D. Dent, copyright CAB International (2000). Additionally, for more detailed information consult “Handbook of Pest Control—The Behavior, Life History, and Control of Household Pests” by Arnold Mallis, 9th Edition, copyright 2004 by GIE Media Inc.

Other Formulation Components

Generally, when the molecules disclosed in Formula One are used in a formulation, such formulation can also contain other components. These components include, but are not limited to, (this is a non-exhaustive and non-mutually exclusive list) wetters, spreaders, stickers, penetrants, buffers, sequestering agents, drift reduction agents, compatibility agents, anti-foam agents, cleaning agents, and emulsifiers. A few components are described forthwith.

A wetting agent is a substance that when added to a liquid increases the spreading or penetration power of the liquid by reducing the interfacial tension between the liquid and the surface on which it is spreading. Wetting agents are used for two main functions in agrochemical formulations: during processing and manufacture to increase the rate of wetting of powders in water to make concentrates for soluble liquids or suspension concentrates; and during mixing of a product with water in a spray tank to reduce the wetting time of wettable powders and to improve the penetration of water into water-dispersible granules. Examples of wetting agents used in wettable powder, suspension concentrate, and water-dispersible granule formulations are: sodium lauryl sulfate; sodium dioctyl sulfosuccinate; alkyl phenol ethoxylates; and aliphatic alcohol ethoxylates.

A dispersing agent is a substance which adsorbs onto the surface of particles and helps to preserve the state of dispersion of the particles and prevents them from reaggregating. Dispersing agents are added to agrochemical formulations to facilitate dispersion and suspension during manufacture, and to ensure the particles redisperse into water in a spray tank. They are widely used in wettable powders, suspension concentrates and water-dispersible granules. Surfactants that are used as dispersing agents have the ability to adsorb strongly onto a particle surface and provide a charged or steric barrier to reaggregation of particles. The most commonly used surfactants are anionic, non-ionic, or mixtures of the two types. For wettable powder formulations, the most common dispersing agents are sodium lignosulfonates. For suspension concentrates, very good adsorption and stabilization are obtained using polyelectrolytes, such as sodium naphthalene sulfonate formaldehyde condensates. Tristyrylphenol ethoxylate phosphate esters are also used. Non-ionics such as alkylarylethylene oxide condensates and EO-PO block copolymers are sometimes combined with anionics as dispersing agents for suspension concentrates. In recent years, new types of very high molecular weight polymeric surfactants have been developed as dispersing agents. These have very long hydrophobic ‘backbones’ and a large number of ethylene oxide chains forming the ‘teeth’ of a ‘comb’ surfactant. These high molecular weight polymers can give very good long-term stability to suspension concentrates because the hydrophobic backbones have many anchoring points onto the particle surfaces. Examples of dispersing agents used in agrochemical formulations are: sodium lignosulfonates; sodium naphthalene sulfonate formaldehyde condensates; tristyrylphenol ethoxylate phosphate esters; aliphatic alcohol ethoxylates; alkyl ethoxylates; EO-PO block copolymers; and graft copolymers.

An emulsifying agent is a substance which stabilizes a suspension of droplets of one liquid phase in another liquid phase. Without the emulsifying agent the two liquids would separate into two immiscible liquid phases. The most commonly used emulsifier blends contain alkylphenol or aliphatic alcohol with twelve or more ethylene oxide units and the oil-soluble calcium salt of dodecylbenzenesulfonic acid. A range of hydrophile-lipophile balance (“HLB”) values from 8 to 18 will normally provide good stable emulsions. Emulsion stability can sometimes be improved by the addition of a small amount of an EO-PO block copolymer surfactant.

A solubilizing agent is a surfactant which will form micelles in water at concentrations above the critical micelle concentration. The micelles are then able to dissolve or solubilize water-insoluble materials inside the hydrophobic part of the micelle. The types of surfactants usually used for solubilization are non-ionics, sorbitan monooleates, sorbitan monooleate ethoxylates, and methyl oleate esters.

Surfactants are sometimes used, either alone or with other additives such as mineral or vegetable oils as adjuvants to spray-tank mixes to improve the biological performance of the pesticide on the target. The types of surfactants used for bioenhancement depend generally on the nature and mode of action of the pesticide. However, they are often non-ionics such as: alkyl ethoxylates; linear aliphatic alcohol ethoxylates; aliphatic amine ethoxylates.

A carrier or diluent in an agricultural formulation is a material added to the pesticide to give a product of the required strength. Carriers are usually materials with high absorptive capacities, while diluents are usually materials with low absorptive capacities. Carriers and diluents are used in the formulation of dusts, wettable powders, granules and water-dispersible granules.

Organic solvents are used mainly in the formulation of emulsifiable concentrates, oil-in-water emulsions, suspoemulsions, and ultra-low volume formulations, and to a lesser extent, granular formulations. Sometimes mixtures of solvents are used. The first main groups of solvents are aliphatic paraffinic oils such as kerosene or refined paraffins. The second main group (and the most common) comprises the aromatic solvents such as xylene and higher molecular weight fractions of C9 and C10 aromatic solvents. Chlorinated hydrocarbons are useful as cosolvents to prevent crystallization of pesticides when the formulation is emulsified into water. Alcohols are sometimes used as cosolvents to increase solvent power. Other solvents may include vegetable oils, seed oils, and esters of vegetable and seed oils.

Thickeners or gelling agents are used mainly in the formulation of suspension concentrates, emulsions and suspoemulsions to modify the rheology or flow properties of the liquid and to prevent separation and settling of the dispersed particles or droplets. Thickening, gelling, and anti-settling agents generally fall into two categories, namely water-insoluble particulates and water-soluble polymers. It is possible to produce suspension concentrate formulations using clays and silicas. Examples of these types of materials, include, but are not limited to, montmorillonite, bentonite, magnesium aluminum silicate, and attapulgite. Water-soluble polysaccharides have been used as thickening-gelling agents for many years. The types of polysaccharides most commonly used are natural extracts of seeds and seaweeds or are synthetic derivatives of cellulose. Examples of these types of materials include, but are not limited to, guar gum; locust bean gum; carrageenam; alginates; methyl cellulose; sodium carboxymethyl cellulose (SCMC); hydroxyethyl cellulose (HEC). Other types of anti-settling agents are based on modified starches, polyacrylates, polyvinyl alcohol and polyethylene oxide. Another good anti-settling agent is xanthan gum.

Microorganisms can cause spoilage of formulated products. Therefore preservation agents are used to eliminate or reduce their effect. Examples of such agents include, but are not limited to: propionic acid and its sodium salt; sorbic acid and its sodium or potassium salts; benzoic acid and its sodium salt; p-hydroxybenzoic acid sodium salt; methyl p-hydroxybenzoate; and 1,2-benzisothiazolin-3-one (BIT).

The presence of surfactants often causes water-based formulations to foam during mixing operations in production and in application through a spray tank. In order to reduce the tendency to foam, anti-foam agents are often added either during the production stage or before filling into bottles. Generally, there are two types of anti-foam agents, namely silicones and non-silicones. Silicones are usually aqueous emulsions of dimethyl polysiloxane, while the non-silicone anti-foam agents are water-insoluble oils, such as octanol and nonanol, or silica. In both cases, the function of the anti-foam agent is to displace the surfactant from the air-water interface.

“Green” agents (e.g., adjuvants, surfactants, solvents) can reduce the overall environmental footprint of crop protection formulations. Green agents are biodegradable and generally derived from natural and/or sustainable sources, e.g. plant and animal sources. Specific examples are: vegetable oils, seed oils, and esters thereof, also alkoxylated alkyl polyglucosides.

For further information, see “Chemistry and Technology of Agrochemical Formulations” edited by D. A. Knowles, copyright 1998 by Kluwer Academic Publishers. Also see “Insecticides in Agriculture and Environment—Retrospects and Prospects” by A. S. Perry, I. Yamamoto, I. Ishaaya, and R. Perry, copyright 1998 by Springer-Verlag.

Pests

In general, the molecules of Formula One may be used to control pests e.g. beetles, earwigs, cockroaches, flies. aphids, scales, whiteflies, leafhoppers, ants, wasps, termites, moths, butterflies, lice, grasshoppers, locusts, crickets, fleas, thrips, bristletails, mites, ticks, nematodes, and symphylans.

In another embodiment, the molecules of Formula One may be used to control pests in the Phyla Nematoda and/or Arthropoda.

In another embodiment, the molecules of Formula One may be used to control pests in the Subphyla Chelicerata, Myriapoda, and/or Hexapoda.

In another embodiment, the molecules of Formula One may be used to control pests in the Classes of Arachnida, Symphyla, and/or Insecta.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Anoplura. A non-exhaustive list of particular genera includes, but is not limited to, Haematopinus spp., Hoplopleura spp., Linognathus spp., Pediculus spp., and Polyplax spp. A non-exhaustive list of particular species includes, but is not limited to, Haematopinus asini, Haematopinus suis, Linognathus setosus, Linognathus ovillus, Pediculus humanus capitis, Pediculus humanus humanus, and Pthirus pubis.

In another embodiment, the molecules of Formula One may be used to control pests in the Order Coleoptera. A non-exhaustive list of particular genera includes, but is not limited to, Acanthoscelides spp., Agriotes spp., Anthonomus spp., Apion spp., Apogonia spp., Aulacophora spp., Bruchus spp., Cerosterna spp., Cerotoma spp., Ceutorhynchus spp., Chaetocnema spp., Colaspis spp., Ctenicera spp., Curculio spp., Cyclocephala spp., Diabrotica spp., Hypera spp., Ips spp., Lyctus spp., Megascelis spp., Meligethes spp., Otiorhynchus spp., Pantomorus spp., Phyllophaga spp., Phyllotreta spp., Rhizotrogus spp., Rhynchites spp., Rhynchophorus spp., Scolytus spp., Sphenophorus spp., Sitophilus spp., and Tribolium spp. A non-exhaustive list of particular species includes, but is not limited to, Acanthoscelides obtectus, Agrilus planipennis, Anoplophora glabripennis, Anthonomus grandis, Ataenius spretulus, Atomaria linearis, Bothynoderes punctiventris, Bruchus pisorum, Callosobruchus maculatus, Carpophilus hemipterus, Cassida vittata, Cerotoma trifurcata, Ceutorhynchus assimilis, Ceutorhynchus napi, Conoderus scalaris, Conoderus stigmosus, Conotrachelus nenuphar, Cotinis nitida, Crioceris asparagi, Cryptolestes ferrugineus, Cryptolestes pusillus, Cryptolestes turcicus, Cylindrocopturus adspersus, Deporaus marginatus, Dermestes lardarius, Dermestes maculatus, Epilachna varivestis, Faustinus cubae, Hylobius pales, Hypera postica, Hypothenemus hampei, Lasioderma serricorne, Leptinotarsa decemlineata, Liogenys fiiscus, Liogenys suturalis, Lissorhoptrus oryzophilus, Maecolaspis joliveti, Melanotus communis, Meligethes aeneus, Melolontha melolontha, Oberea brevis, Oberea linearis, Oryctes rhinoceros, Oryzaephilus mercator, Oryzaephilus surinamensis, Oulema melanopus, Oulema oryzae, Phyllophaga cuyabana, Popillia japonica, Prostephanus truncatus, Rhyzopertha dominica, Sitona lineatus, Sitophilus granarius, Sitophilus oryzae, Sitophilus zeamais, Stegobium paniceum, Tribolium castaneum, Tribolium confusum, Trogoderma variabile, and Zabrus tenebrioides.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Dermaptera.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Blattaria. A non-exhaustive list of particular species includes, but is not limited to, Blattella germanica, Blatta orientalis, Parcoblatta pennsylvanica, Periplaneta americana, Periplaneta australasiae, Periplaneta brunnea, Periplaneta fuliginosa, Pycnoscelus surinamensis, and Supella longipalpa.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Diptera. A non-exhaustive list of particular genera includes, but is not limited to, Aedes spp., Agromyza spp., Anastrepha spp., Anopheles spp., Bactrocera spp., Ceratitis spp., Chrysops spp., Cochliomyia spp., Contarinia spp., Culex spp., Dasineura spp., Delia spp., Drosophila spp., Fannia spp., Hylemyia spp., Liriomyza spp., Musca spp., Phorbia spp., Tabanus spp., and Tipula spp. A non-exhaustive list of particular species includes, but is not limited to, Agromyza frontella, Anastrepha suspensa, Anastrepha ludens, Anastrepha obliqa, Bactrocera cucurbitae, Bactrocera dorsalis, Bactrocera invadens, Bactrocera zonata, Ceratitis capitata, Dasineura brassicae, Delia platura, Fannia canicularis, Fannia scalaris, Gasterophilus intestinalis, Gracillia perseae, Haematobia irritans, Hypoderma lineatum, Liriomyza brassicae, Melophagus ovinus, Musca autumnalis, Musca domestica, Oestrus ovis, Oscinella frit, Pegomya betae, Psila rosae, Rhagoletis cerasi, Rhagoletis pomonella, Rhagoletis mendax, Sitodiplosis mosellana, and Stomoxys calcitrans.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Hemiptera. A non-exhaustive list of particular genera includes, but is not limited to, Adelges spp., Aulacaspis spp., Aphrophora spp., Aphis spp., Bemisia spp., Ceroplastes spp., Chionaspis spp., Chrysomphalus spp., Coccus spp., Empoasca spp., Lepidosaphes spp., Lagynotomus spp., Lygus spp., Macrosiphum spp., Nephotettix spp., Nezara spp., Philaenus spp., Phytocoris spp., Piezodorus spp., Planococcus spp., Pseudococcus spp., Rhopalosiphum spp., Saissetia spp., Therioaphis spp., Toumeyella spp., Toxoptera spp., Trialeurodes spp., Triatoma spp. and Unaspis spp. A non-exhaustive list of particular species includes, but is not limited to, Acrosternum hilare, Acyrthosiphon pisum, Aleyrodes proletella, Aleurodicus dispersus, Aleurothrixus floccosus, Amrasca biguttula biguttula, Aonidiella aurantii, Aphis gossypii, Aphis glycines, Aphis pomi, Aulacorthum solani, Bemisia argentifolii, Bemisia tabaci, Blissus leucopterus, Brachycorynella asparagi, Brevennia rehi, Brevicoryne brassicae, Calocoris norvegicus, Ceroplastes rubens, Cimex hemipterus, Cimex lectularius, Dagbertus fasciatus, Dichelops furcatus, Diuraphis noxia, Diaphorina citri, Dysaphis plantaginea, Dysdercus suturellus, Edessa meditabunda, Eriosoma lanigerum, Eurygaster maura, Euschistus heros, Euschistus servus, Helopeltis antonii, Helopeltis theivora, Icerya purchasi, Idioscopus nitidulus, Laodelphax striatellus, Leptocorisa oratorius, Leptocorisa varicornis, Lygus hesperus, Maconellicoccus hirsutus, Macrosiphum euphorbiae, Macrosiphum granarium, Macrosiphum rosae, Macrosteles quadrilineatus, Mahanarva frimbiolata, Metopolophium dirhodum, Mictis longicornis, Myzus persicae, Nephotettix cinctipes, Neurocolpus longirostris, Nezara viridula, Nilaparvata lugens, Parlatoria pergandii, Parlatoria ziziphi, Peregrinus maidis, Phylloxera vitifoliae, Physokermes piceae, Phytocoris califomicus, Phytocoris relativus, Piezodorus guildinii, Poecilocapsus lineatus, Psallus vaccinicola, Pseudacysta perseae, Pseudococcus brevipes, Quadraspidiotus perniciosus, Rhopalosiphum maidis, Rhopalosiphum padi, Saissetia oleae, Scaptocoris castanea, Schizaphis graminum, Sitobion avenae, Sogatella furcifera, Trialeurodes vaporariorum, Trialeurodes abutiloneus, Unaspis yanonensis, and Zulia entrerriana.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Hymenoptera. A non-exhaustive list of particular genera includes, but is not limited to, Acromyrmex spp., Atta spp., Camponotus spp., Diprion spp., Formica spp., Monomorium spp., Neodiprion spp., Pogonomyrmex spp., Polistes spp., Solenopsis spp., Vespula spp., and Xylocopa spp. A non-exhaustive list of particular species includes, but is not limited to, Athalia rosae, Atta texana, Iridomyrmex humilis, Monomorium minimum, Monomorium pharaonis, Solenopsis invicta, Solenopsis geminata, Solenopsis molesta, Solenopsis richtery, Solenopsis xyloni, and Tapinoma sessile.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Isoptera. A non-exhaustive list of particular genera includes, but is not limited to, Coptotermes spp., Cornitermes spp., Cryptotermes spp., Heterotermes spp., Kalotermes spp., Incisitermes spp., Macrotermes spp., Marginitermes spp., Microcerotermes spp., Procornitermes spp., Reticulitermes spp., Schedorhinotermes spp., and Zootermopsis spp. A non-exhaustive list of particular species includes, but is not limited to, Coptotermes curvignathus, Coptotermes frenchi, Coptotermes formosanus, Heterotermes aureus, Microtermes obesi, Reticulitermes banyulensis, Reticulitermes grassei, Reticulitermes flavipes, Reticulitermes hageni, Reticulitermes hesperus, Reticulitermes santonensis, Reticulitermes speratus, Reticulitermes tibialis, and Reticulitermes virginicus.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Lepidoptera. A non-exhaustive list of particular genera includes, but is not limited to, Adoxophyes spp., Agrotis spp., Argyrotaenia spp., Cacoecia spp., Caloptilia spp., Chilo spp., Chrysodeixis spp., Colias spp., Crambus spp., Diaphania spp., Diatraea spp., Earias spp., Ephestia spp., Epimecis spp., Feltia spp., Gortyna spp., Helicoverpa spp., Heliothis spp., Indarbela spp., Lithocolletis spp., Loxagrotis spp., Malacosoma spp., Peridroma spp., Phyllonorycter spp., Pseudaletia spp., Sesamia spp., Spodoptera spp., Synanthedon spp., and Yponomeuta spp. A non-exhaustive list of particular species includes, but is not limited to, Achaea janata, Adoxophyes orana, Agrotis ipsilon, Alabama argillacea, Amorbia cuneana, Amyelois transitella, Anacamptodes defectaria, Anarsia lineatella, Anomis sabulifera, Anticarsia gemmatalis, Archips argyrospila, Archips rosana, Argyrotaenia citrana, Autographa gamma, Bonagota cranaodes, Borbo cinnara, Bucculatrix thurberiella, Capua reticulana, Carposina niponensis, Chlumetia transversa, Choristoneura rosaceana, Cnaphalocrocis medinalis, Conopomorpha cramerella, Cossus cossus, Cydia caryana, Cydia funebrana, Cydia molesta, Cydia nigricana, Cydia pomonella, Darna diducta, Diatraea saccharalis, Diatraea grandiosella, Earias insulana, Earias vittella, Ecdytolopha aurantianum, Elasmopalpus lignosellus, Ephestia cautella, Ephestia elutella, Ephestia kuehniella, Epinotia aporema, Epiphyas postvittana, Erionota thrax, Eupoecilia ambiguella, Euxoa auxiliaris, Grapholita molesta, Hedylepta indicata, Helicoverpa armigera, Helicoverpa zea, Heliothis virescens, Hellula undalis, Keiferia lycopersicella, Leucinodes orbonalis, Leucoptera coffeella, Leucoptera malifoliella, Lobesia botrana, Loxagrotis albicosta, Lymantria dispar, Lyonetia clerkella, Mahasena corbetti, Mamestra brassicae, Maruca testulalis, Metisa plana, Mythimna unipuncta, Neoleucinodes elegantalis, Nymphula depunctalis, Operophtera brumata, Ostrinia nubilalis, Oxydia vesulia, Pandemis cerasana, Pandemis heparana, Papilio demodocus, Pectinophora gossypiella, Peridroma saucia, Perileucoptera coffeella, Phthorimaea operculella, Phyllocnistis citrella, Pieris rapae, Plathypena scabra, Plodia interpunctella, Plutella xylostella, Polychrosis viteana, Prays endocarpa, Prays oleae, Pseudaletia unipuncta, Pseudoplusia includens, Rachiplusia nu, Scirpophaga incertulas, Sesamia inferens, Sesamia nonagrioides, Setora nitens, Sitotroga cerealella, Sparganothis pilleriana, Spodoptera exigua, Spodoptera frugiperda, Spodoptera eridania, Thecla basilides, Tineola bisselliella, Trichoplusia ni, Tuta absoluta, Zeuzera coffeae, and Zeuzera pyrina.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Mallophaga. A non-exhaustive list of particular genera includes, but is not limited to, Anaticola spp., Bovicola spp., Chelopistes spp., Goniodes spp., Menacanthus spp., and Trichodectes spp. A non-exhaustive list of particular species includes, but is not limited to, Bovicola bovis, Bovicola caprae, Bovicola ovis, Chelopistes meleagridis, Goniodes dissimilis, Goniodes gigas, Menacanthus stramineus, Menopon gallinae, and Trichodectes canis.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Orthoptera. A non-exhaustive list of particular genera includes, but is not limited to, Melanoplus spp., and Pterophylla spp. A non-exhaustive list of particular species includes, but is not limited to, Anabrus simplex, Gryllotalpa africana, Gryllotalpa australis, Gryllotalpa brachyptera, Gryllotalpa hexadactyla, Locusta migratoria, Microcentrum retinerve, Schistocerca gregaria, and Scudderia furcata.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Siphonaptera. A non-exhaustive list of particular species includes, but is not limited to, Ceratophyllus gallinae, Ceratophyllus niger, Ctenocephalides canis, Ctenocephalides felis, and Pulex irritans.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Thysanoptera. A non-exhaustive list of particular genera includes, but is not limited to, Caliothrips spp., Frankliniella spp., Scirtothrips spp., and Thrips spp. A non-exhaustive list of particular sp. includes, but is not limited to, Frankliniella fitsca, Frankliniella occidentalis, Frankliniella schultzei, Frankliniella williamsi, Heliothrips haemorrhoidalis, Rhipiphorothrips cruentatus, Scirtothrips citri, Scirtothrips dorsalis, and Taeniothrips rhopalantennalis, Thrips hawaiiensis, Thrips nigropilosus, Thrips orientalis, Thrips tabaci.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Thysanura. A non-exhaustive list of particular genera includes, but is not limited to, Lepisma spp. and Thermobia spp.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Acarina. A non-exhaustive list of particular genera includes, but is not limited to, Acarus spp., Aculops spp., Boophilus spp., Demodex spp., Dermacentor spp., Epitrimerus spp., Eriophyes spp., Ixodes spp., Oligonychus spp., Panonychus spp., Rhizoglyphus spp., and Tetranychus spp. A non-exhaustive list of particular species includes, but is not limited to, Acarapis woodi, Acarus siro, Aceria mangiferae, Aculops lycopersici, Aculus pelekassi, Aculus schlechtendali, Amblyomma americanum, Brevipalpus obovatus, Brevipalpus phoenicis, Dermacentor variabilis, Dermatophagoides pteronyssinus, Eotetranychus carpini, Notoedres cati, Oligonychus coffeae, Oligonychus ilicis, Panonychus citri, Panonychus ulmi, Phyllocoptruta oleivora, Polyphagotarsonemus latus, Rhipicephalus sanguineus, Sarcoptes scabiei, Tegolophus perseaflorae, Tetranychus urticae, and Varroa destructor.

In another embodiment, the molecules of Formula One may be used to control pest of the Order Symphyla. A non-exhaustive list of particular sp. includes, but is not limited to, Scutigerella immaculata.

In another embodiment, the molecules of Formula One may be used to control pests of the Phylum Nematoda. A non-exhaustive list of particular genera includes, but is not limited to, Aphelenchoides spp., Belonolaimus spp., Criconemella spp., Ditylenchus spp., Heterodera spp., Hirschmanniella spp., Hoplolaimus spp., Meloidogyne spp., Pratylenchus spp., and Radopholus spp. A non-exhaustive list of particular sp. includes, but is not limited to, Dirofilaria immitis, Heterodera zeae, Meloidogyne incognita, Meloidogyne javanica, Onchocerca volvulus, Radopholus similis, and Rotylenchulus reniformis.

For additional information consult “HANDBOOK OF PEST CONTROL—THE BEHAVIOR, LIFE HISTORY, AND CONTROL OF HOUSEHOLD PESTS” by Arnold Mallis, 9th Edition, copyright 2004 by GIE Media Inc.

Applications

Molecules of Formula One are generally used in amounts from about 0.01 grams per hectare to about 5000 grams per hectare to provide control. Amounts from about 0.1 grams per hectare to about 500 grams per hectare are generally preferred, and amounts from about 1 gram per hectare to about 50 grams per hectare are generally more preferred.

The area to which a molecule of Formula One is applied can be any area inhabited (or maybe inhabited, or traversed by) a pest, for example: where crops, trees, fruits, cereals, fodder species, vines, turf and ornamental plants, are growing; where domesticated animals are residing; the interior or exterior surfaces of buildings (such as places where grains are stored), the materials of construction used in building (such as impregnated wood), and the soil around buildings. Particular crop areas to use a molecule of Formula One include areas where apples, corn, sunflowers, cotton, soybeans, canola, wheat, rice, sorghum, barley, oats, potatoes, oranges, alfalfa, lettuce, strawberries, tomatoes, peppers, crucifers, pears, tobacco, almonds, sugar beets, beans and other valuable crops are growing or the seeds thereof are going to be planted. It is also advantageous to use ammonium sulfate with a molecule of Formula One when growing various plants.

Controlling pests generally means that pest populations, pest activity, or both, are reduced in an area. This can come about when: pest populations are repulsed from an area; when pests are incapacitated in or around an area; or pests are exterminated, in whole, or in part, in or around an area. Of course, a combination of these results can occur. Generally, pest populations, activity, or both are desirably reduced more than fifty percent, preferably more than 90 percent. Generally, the area is not in or on a human; consequently, the locus is generally a non-human area.

The molecules of Formula One may be used in mixtures, applied simultaneously or sequentially, alone or with other compounds to enhance plant vigor (e.g. to grow a better root system, to better withstand stressful growing conditions). Such other compounds are, for example, compounds that modulate plant ethylene receptors, most notably 1-methylcyclopropene (also known as 1-MCP). Furthermore, such molecules may be used during times when pest activity is low, such as before the plants that are growing begin to produce valuable agricultural commodities. Such times include the early planting season when pest pressure is usually low.

The molecules of Formula One can be applied to the foliar and fruiting portions of plants to control pests. The molecules will either come in direct contact with the pest, or the pest will consume the pesticide when eating leaf, fruit mass, or extracting sap, that contains the pesticide. The molecules of Formula One can also be applied to the soil, and when applied in this manner, root and stem feeding pests can be controlled. The roots can absorb a molecule taking it up into the foliar portions of the plant to control above ground chewing and sap feeding pests.

Generally, with baits, the baits are placed in the ground where, for example, termites can come into contact with, and/or be attracted to, the bait. Baits can also be applied to a surface of a building, (horizontal, vertical, or slant surface) where, for example, ants, termites, cockroaches, and flies, can come into contact with, and/or be attracted to, the bait. Baits can comprise a molecule of Formula One.

The molecules of Formula One can be encapsulated inside, or placed on the surface of a capsule. The size of the capsules can range from nanometer size (about 100-900 nanometers in diameter) to micrometer size (about 10-900 microns in diameter).

Because of the unique ability of the eggs of some pests to resist certain pesticides, repeated applications of the molecules of Formula One may be desirable to control newly emerged larvae.

Systemic movement of pesticides in plants may be utilized to control pests on one portion of the plant by applying (for example by spraying an area) the molecules of Formula One to a different portion of the plant. For example, control of foliar-feeding insects can be achieved by drip irrigation or furrow application, by treating the soil with for example pre- or post-planting soil drench, or by treating the seeds of a plant before planting.

Seed treatment can be applied to all types of seeds, including those from which plants genetically modified to express specialized traits will germinate. Representative examples include those expressing proteins toxic to invertebrate pests, such as Bacillus thuringiensis or other insecticidal toxins, those expressing herbicide resistance, such as “Roundup Ready” seed, or those with “stacked” foreign genes expressing insecticidal toxins, herbicide resistance, nutrition-enhancement, drought resistance, or any other beneficial traits. Furthermore, such seed treatments with the molecules of Formula One may further enhance the ability of a plant to better withstand stressful growing conditions. This results in a healthier, more vigorous plant, which can lead to higher yields at harvest time. Generally, about 1 gram of the molecules of Formula One to about 500 grams per 100,000 seeds is expected to provide good benefits, amounts from about 10 grams to about 100 grams per 100,000 seeds is expected to provide better benefits, and amounts from about 25 grams to about 75 grams per 100,000 seeds is expected to provide even better benefits.

It should be readily apparent that the molecules of Formula One may be used on, in, or around plants genetically modified to express specialized traits, such as Bacillus thuringiensis or other insecticidal toxins, or those expressing herbicide resistance, or those with “stacked” foreign genes expressing insecticidal toxins, herbicide resistance, nutrition-enhancement, or any other beneficial traits.

The molecules of Formula One may be used for controlling endoparasites and ectoparasites in the veterinary medicine sector or in the field of non-human animal keeping. The molecules of Formula One are applied, such as by oral administration in the form of, for example, tablets, capsules, drinks, granules, by dermal application in the form of, for example, dipping, spraying, pouring on, spotting on, and dusting, and by parenteral administration in the form of, for example, an injection.

The molecules of Formula One may also be employed advantageously in livestock keeping, for example, cattle, sheep, pigs, chickens, and geese. They may also be employed advantageously in pets such as, horses, dogs, and cats. Particular pests to control would be fleas and ticks that are bothersome to such animals. Suitable formulations are administered orally to the animals with the drinking water or feed. The dosages and formulations that are suitable depend on the species.

The molecules of Formula One may also be used for controlling parasitic worms, especially of the intestine, in the animals listed above.

The molecules of Formula One may also be employed in therapeutic methods for human health care. Such methods include, but are limited to, oral administration in the form of, for example, tablets, capsules, drinks, granules, and by dermal application.

Pests around the world have been migrating to new environments (for such pest) and thereafter becoming a new invasive species in such new environment. The molecules of Formula One may also be used on such new invasive species to control them in such new environment.

The molecules of Formula One may also be used in an area where plants, such as crops, are growing (e.g. pre-planting, planting, pre-harvesting) and where there are low levels (even no actual presence) of pests that can commercially damage such plants. The use of such molecules in such area is to benefit the plants being grown in the area. Such benefits, may include, but are not limited to, improving the health of a plant, improving the yield of a plant (e.g. increased biomass and/or increased content of valuable ingredients), improving the vigor of a plant (e.g. improved plant growth and/or greener leaves), improving the quality of a plant (e.g. improved content or composition of certain ingredients), and improving the tolerance to abiotic and/or biotic stress of the plant.

Before a pesticide can be used or sold commercially, such pesticide undergoes lengthy evaluation processes by various governmental authorities (local, regional, state, national, and international). Voluminous data requirements are specified by regulatory authorities and must be addressed through data generation and submission by the product registrant or by a third party on the product registrant's behalf, often using a computer with a connection to the World Wide Web. These governmental authorities then review such data and if a determination of safety is concluded, provide the potential user or seller with product registration approval. Thereafter, in that locality where the product registration is granted and supported, such user or seller may use or sell such pesticide.

A molecule according to Formula One can be tested to determine its efficacy against pests. Furthermore, mode of action studies can be conducted to determine if said molecule has a different mode of action than other pesticides. Thereafter, such acquired data can be disseminated, such as by the internet, to third parties.

The headings in this document are for convenience only and must not be used to interpret any portion hereof.

TABLE SECTION % Control (or Mortality) Rating BAW, CEW & CL Rating Table 50-100 A More than 0-Less than 50 B Not Tested C No activity noticed in this bioassay D GPA Rating Table 80-100 A More than 0-Less than 80 B Not Tested C No activity noticed in this bioassay D

TABLE 1 Structures for Compounds Compound Number Structure AI34

AI36

AI37

AI38

AI39

AI40

AI41

AI44

AI45

AC1

AC2

AC3

AC4

AC5

AC6

AC7

AC8

AC9

AC10

AC11

AC12

AC13

AC14

AC15

AC16

AC17

AC18

AC19

AC20

AC21

AC22

AC23

AC24

AC25

AC26

AC27

AC28

AC29

AC30

AC31

AC32

AC33

AC34

AC35

AC36

AC37

AC38

AC39

AC40

AC41

AC42

AC43

AC44

AC45

AC46

AC47

AC48

AC49

AC50

AC51

AC52

AC53

AC54

AC57

AC58

AC59

AC60

AC61

AC62

AC63

AC64

AC65

AC66

AC67

AC68

AC69

AC70

AC71

AC72

AC75

AC76

AC77

AC78

AC79

AC80

AC81

AC82

AC83

AC84

AC85

AC86

AC87

AC89

AC90

AC91

AC92

AC93

AC94

AC95

AC96

AC97

AC98

AC99

AC100

AC101

AC102

AC103

AC104

AC105

AC106

AC107

AC108

AC109

AC110

AC111

AC112

AC113

AC114

AC115

AC116

AC117

AC118

BC1

BC2

BC3

BC4

BC5

BC6

BC7

BC8

BC9

BC10

BC11

BC12

BC13

BC14

CI4

CI5

CI8

CI9

CI34

CI35

CI36

CI37

CI38

CI39

CI40

CI41

CI49

CI50

CI51

CI52

CI53

CI54

CI55

CI56

CI57

CC1

CC2

CC3

CC4

CC5

CC6

CC7

CC8

CC9

CC10

CC11

CC12

CC13

CC14

CC15

CC16

CC17

CC18

CC19

CC20

CC21

CC22

CC23

CC24

CC25

CC26

CC27

CC28

CC29

CC30

CC31

CC32

CC33

CC34

CC35

CC36

CC37

CC38

CC39

CC40

CC41

CC42

CC43

CC44

CC45

CC46

CC47

CC48

CC49

CC50

CC51

CC52

CC53

CC54

DC1

DC2

DC3

DC4

DC5

DC6

DC7

DC8

DC9

DC10

DC11

DC12

DC13

DC14

DC15

DC16

DC17

DC18

DC19

DC20

DC21

DC22

DC23

DC24

DC25

DC26

DC27

DC28

DC29

DC30

DC31

DC32

DC33

DC34

DC35

DC36

DC37

DC38

DC39

DC40

DC41

DC42

DC43

DC44

DC45

DC46

DC47

DC48

DC49

DC50

DC51

DC52

DC53

DC54

DC55

DC56

DC57

DC58

DC59

DC60

DC61

DC62

DC63

DC64

DC65

DC66

DC67

DC68

DC69

DC70

TABLE 1A Structures for F Compounds Prepared as Compound in Number Structure Appearance Example: F1

brown solid 128 F2

off-white solid 15 F3

light green gum 15 F4

brown gum 15 F5

off-white solid 15 F6

pale yellow solid 133 F7

white solid 129 F8

yellow solid 128 F8A

yellow solid 134 F8B

off-white solid 134

TABLE 1B Structures of Prophetic Compounds Subsequently Exemplified Prepared as Compound in Number Structure Appearance Example: P31

oil 129 P65

off-white solid 128 P108

brown gum 128 P110

pale brown solid 128 P153

brown gum 128 P155

brown gum 128 P198

yellow solid 128 P200

pale yellow solid 128 P243

brown gummy liquid 128 P245

brown gummy liquid 128 P333

off white solid 128 P335

brown solid 128 P336

pale brown solid 128 P378

brown solid 128 P380

brown gum 128 P423

pale yellow solid 128 P425

pale yellow solid 128 P468

brown semi solid 128 P470

brown gum 128 P513

brown gummy liquid 128 P515

yellow solid 128 P693

pale brown solid 128 P1003

brown solid 128 P1005

off white solid 128 P1009

dark brown solid 128 P1010

yellow solid 128 P1011

pale yellow solid 128 P1015

brown solid 128 P1020

brown solid 128 P1023

brown semi solid 128 P1025

pale brown solid 128 P1026

brown gummy solid 128 P1033

brown gum 128 P1035

brown solid 128 P1043

brown gummy solid 128 P1045

pale green solid 128 P1048

brown gummy liquid 128 P1050

off white solid 128 P1093

yellow gum 128 P1095

brown gum 128 P1183

off white solid 128 P1198

brown semi solid 128 P1193

brown solid 128 P1195

brown gum 128 P1200

brown solid 128 P1213

brown solid 128

TABLE 2 Analytical Data for Compounds in Table 1. Compound Number mp (° C.) ESIMS ¹H NMR (δ)^(a) IR (cm⁻¹) AC1 156- 386.09 7.83 (m, 2H), 7.68-7.63 161 ([M − H]⁻) (m, 5H), 6.93 (dd, J = 15.6, 8.0 Hz, 1H), 6.81 (d J = 15.6 Hz, 1H,), 4.15 (m, 1H), 2.80 (s, 3H) AC2 110- 374 7.80 (d, J = 8.4 Hz, 2H), 112 ([M + H]⁺) 7.48 (d, J = 8.0 Hz, 2H), 7.38 (m, 1H), 7.30 (s, 2H), 6.65 (d, J = 16.0 Hz, 1H), 6.46 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H) AC3 162- 402.24 7.42 (m, 4H), 7.37 (t, J = 166 ([M + H]⁺) 1.8 Hz, 1H), 7.28 (s, 2H), 6.63 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 8.4 Hz, 1H), 4.15 (m, 1H), 3.20 (s, 3H), 3.00 (s, 3H) AC4 122- 454 7.79 (d, J = 1.2 Hz, 2H), 126 ([M − H]⁻) 7.48 (d, J = 8.4 Hz, 2H), 7.38 (t, J = 1.8 Hz, 1H), 7.30 (s, 2H), 6.64 (d, J = 15.6 Hz, 1H), 6.40 (dd, J = 15.6, 8.0 Hz, 1H), 6.30 (m, 1H), 4.15 (m, 3H) AC5 444.12 7.67 (s, 3H), 7.64 (d, J = ([M + H]⁺) 8.0 Hz, 2H), 7.42 (d, J = 8.0 Hz, 2H), 6.91 (dd, J = 15.6, 8.0 Hz, 1H), 6.80 (d, J = 15.6 Hz, 1H), 4.80 (m, 1H), 3.60 (br s, 8H) AC6 468.40 7.40 (m, 2H), 7.26 (m, 1657, 1113, ([M − H]⁻) 3H), 6.56 (d, J = 16.0 804 Hz, 1H), 6.48 (dd, J = 16.0, 8.0 Hz, 1H), 5.82 (br s, 1H), 4.08 (m, 3H), 2.52 (s, 3H) AC7 511.02 8.39 (s, 1H), 7.74 (m, 3276, 1645, ([M − H]⁻) 1H), 7.39 (m, 3H), 7.24 1111, 801 (m, 4H), 6.58 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 8.0 Hz, 1H), 6.16 (br s, 1H), 4.63 (m, 2H), 4.12 (m, 1H), 2.41 (s, 3H) AC8 454.11 7.39 (s, 1H), 7.22 (m, 1748, 1112, ([M − H]⁻) 2H), 7.19 (m, 3H), 6.53 801 (d, J = 16.0 Hz, 1H), 6.39-6.34 (dd, J = 16.0, 8.0 Hz, 1H), 4.22 (m, 1H), 3.95 (t, J = 7.0 Hz, 2H), 2.62 (t, J = 8.0 Hz, 2H), 2.30 (s, 3H), 2.18 (m, 2H) AC9 494.02 7.45 (t, J = 7.6 Hz, 1H), 3276, 1645, ([M − H]⁻) 7.36 (m, 2H), 7.21 (m, 1112, 801 3H), 7.15 (m, 4H), 6.56 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 8.4 Hz, 1H), 6.08 (br s, 1H), 4.68 (d, J = 5.6 Hz, 2H), 4.11 (m, 1H), 2.44 (s, 3H) A10 140- 458.00 7.38 (t, J = 1.6 Hz, 1H), 143 ([M − H]⁻) 7.34 (d, J = 7.6 Hz, 1H), 7.27 (m, 2H), 7.24 (m, 2H), 6.57 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 6.16 (m 1H), 5.44 (m, 1H), 4.12 (m, 1H), 3.51 (m, 2H), 3.40 (m, 2H), 2.44 (s, 3H) AC11 476.17 7.39-7.29 (m, 9H), 7.24 3287, 1644, ([M − H]⁻) (m, 2H), 6.56 (d, J = 1112, 801 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 8.0 Hz, 1H), 5.99 (br s, 1H), 4.63 (d, J = 6.0 Hz, 1H), 4.11 (m, 1H), 2.47 (s, 3H) AC12 479.30 8.63 (d, J = 4.4 Hz, 1H), 3293, 1653, ([M + H]⁺) 7.71 (m, 1H), 7.47 (d, J = 1112, 800 8.4 Hz, 1H), 7.37 (m, 2H), 7.32 (m, 2H), 7.23 (m, 2H), 7.13 (m, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 4.75 (d, J = 4.8 Hz, 2H), 4.12 (m, 1H), 2.49 (s, 3H) AC13 75-78 490.04 7.38 (m, 2H), 7.27 (m, ([M − H]⁻) 3H), 7.23 (br s, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.45 (m 1H), 6.42 (dd, J = 16.0, 8.4 Hz, 1H), 4.91 (m 1H), 4.64 (m, 2H), 4.14 (m, 1H), 4.04 (m, 2H), 2.46 (s, 3H) AC14 480.99 8.63 (s, 2H), 7.76 (d, J = 3293, 1645, ([M + 2H]⁺) 8.0 Hz, 1H), 7.36 (m, 1113, 800 3H), 7.22 (m, 1H), 7.13 (m, 2H), 6.57 (d, J = 16.0 Hz, 1H), 6.39 (dd, J = 16.0, 8.0 Hz, 1H), 6.13 (br s, 1H), 4.66 (d, J = 5.6 Hz, 2H), 4.11 (m, 1H), 2.46 (s, 3H) AC15 59-61 516.86 7.45 (s, 1H), 7.37 (m, 3246, 1635, ([M − H]⁻) 1H), 7.34 (m, 1H), 7.26 1112, 801 (m, 3H), 7.22 (m, 1H), 6.57 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 6.18 (m, 1H), 4.71 (d, J = 6.4 Hz, 2H), 4.11 (m, 1H), 2.46 (s, 3H) AC16 506.93 8.47 (m, 1H), 8.19 (s, 1657, 1113, ([M + H]⁺) 1H), 7.76 (m, 1H), 7.47 801 (m, 2H), 7.37 (m, 1H), 7.28 (m, 2H), 7.24 (m, 1H), 7.21 (m, 1H), 6.59 (d, J = 16.0 Hz, 1H), 6.39 (dd, J = 16.0, 8.4 Hz, 1H), 4.12 (m, 1H), 2.48 (s, 3H), 1.88 (s, 6H) AC17 70-73 494.98 7.49 (m, 2H), 7.38 (m, ([M − H]⁻) 1H), 7.29 (m, 4H), 7.08 (m, 3H), 6.91 (m, 1H), 6.61 (d, J = 16.0 Hz, 1H), 6.48 (m, 1H), 6.43 (dd, J = 16.0, 8.0 Hz, 1H), 4.13 (m, 1H), 2.49 (s, 3H) AC18 155- 480.44 8.73 (d, J = 4.8 Hz, 2H), 158 ([M + H]⁺) 7.53 (d, J = 8.4 Hz, 1H), 7.37 (m, 1H), 7.27 (m, 4H), 7.23 (m, 1H), 7.11 (m, 1H), 6.60 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 8.0 Hz, 1H), 4.90 (d, J = 4.8 Hz, 2H), 4.13 (m, 1H), 2.52 (s, 3H) AC19 55-57 471.66 7.37 (m, 1H), 7.33 (d, J = ([M + H]⁺) 7.6 Hz, 1H), 7.27 (m, 2H), 7.22 (m, 2H), 6.57 (d, J = 16.0 Hz, 1H), 6.39 (dd, J = 16.0, 8.0 Hz, 1H), 6.10 (brs, 1H), 4.13 (m, 2H), 3.94 (m, 1H), 3.79 (m, 2H), 3.35 (m, 1H), 2.45 (s, 3H), 2.14 (m, 1H), 1.71 (m, 2H), 1.65 (m, 1H). AC20 467.68 7.37 (m, 2H), 7.27 (m, 3437, 1664, ([M + H]⁺) 2H), 7.23 (m, 2H), 6.57 1265, 1114, (d, J = 16.0 Hz, 1H), 746 6.38 (m, 3H), 6.01 (m, 1H), 4.63 (d, J = 5.6 Hz, 2H), 4.13 (m, 1H), 2.45 (s, 3H) AC21 61-64 528.78 8.44 (s, 1H), 8.18 (s, ([M + H]⁺) 1H), 7.83 (br s, 1H), 7.38 (m, 2H), 7.27 (m, 2H), 7.25 (m, 2H), 7.21 (m, 1H), 6.57 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 5.01 (s, 2H), 4.11 (m, 1H), 2.43 (s, 3H) AC22 545.08 8.39 (s, 1H), 7.73 (m, 3270, 1642, ([M − H]⁻) 1H), 7.40 (s, 1H), 7.35 1111, 809 (m, 2H), 7.22 (m, 3H), 6.57 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 7.6 Hz, 1H), 6.14 (br s, 1H), 4.62 (d, J = 6.0 Hz, 2H), 4.13 (m, 1H), 2.45 (s, 3H) AC23 492.35 7.42 (s, 2H), 7.36 (m, 3273, 1641, ([M − H]⁻) 1H), 7.24 (m, 2H), 6.59 1250, 1113, (d, J = 16.0 Hz, 1H), 807 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 6.20 (br s, 1H), 5.46 (m, 1H), 4.15 (m, 1H), 3.52 (m, 2H), 3.41 (m, 2H), 2.45 (s, 3H) AC24 129- 526.98 7.40 (m, 2H), 7.27 (m, 3298, 1664, 132 ([M + H]⁺) 2H), 7.25 (m, 2H), 6.92 1113, 803 (br s, 2H), 6.60 (m, 1H), 6.48(dd, J = 16.0, 8.0 Hz, 1H), 4.19 (d, J = 5.2, 2H), 4.08 (m, 1H), 3.99 (m, 2H), 2.46 (s, 3H) AC25 542.24 7.41 (m, 3H), 7.27 (m, 3257, 1652, ([M − H]⁻) 2H), 6.58 (d, J = 15.6 1316, 1109, Hz, 1H), 6.42 (m, 2H), 807 4.92 (m, 1H), 4.65 (m, 2H), 4.14 (m, 1H), 4.09 (m, 2H), 2.46 (s, 3H) AC26 550.69 7.45 (s, 1H), 7.40 (s, 3255, 1638, ([M − H]⁻) 2H), 7.34 (d, J = 8.0 Hz, 1113, 809 1H), 7.22 (m, 2H), 6.54 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 8.0 Hz, 1H), 4.71 (d, J = 6.0 Hz, 2H), 4.11 (m, 1H), 2.46 (s, 3H) AC27 541.00 8.46 (d, J = 4.0 Hz, 1H), 1653, 1113, ([M − H]⁻) 8.20 (s, 1H), 7.76 (m, 809 1H), 7.47 (m, 2H), 7.41 (s, 2H), 7.23 (m, 2H), 7.21 (m, 1H), 6.59 (d, J = 16.0 Hz, 1H), 6.37 (dd, J = 16.0, 8.4 Hz, 1H), 4.11 (m, 1H), 2.48 (s, 3H), 1.88 (s, 6H) AC28 65-67 564.84 8.40 (s, 1H), 7.74 (m, 3267, 1650, ([M − H]⁻) 2H), 7.42 (m, 3H), 7.36 1112, 809 (m, 2H), 6.72 (br s, 1H), 6.52 (d, J = 16.0 Hz, 1H), 6.43 (dd, J = 16.0, 8.0 Hz, 1H), 4.66 (d, J = 6.4 Hz, 2H), 4.12 (m, 1H) AC29 75-78 511.78 7.71 (d, J = 8.4 Hz, 1H), ([M − H]⁻) 7.42 (m, 3H), 7.35 (m, 1H), 6.75 (br s, 1H), 6.56 (d, J = 16.0 Hz, 1H), 6.43 (dd, J = 16.0, 8.0 Hz, 1H), 5.49 (m, 1H), 4.14 (m, 1H), 3.50 (m, 4H) AC30 110- 543.72 7.42 (d, J = 8.4 Hz, 1H), 113 ([M − H]⁻) 7.44 (s, 1H), 7.40 (s, 1H), 7.38 (m, 1H), 7.06 (br s, 1H), 6.58 (d, J = 15.6 Hz, 1H), 6.45 (dd, J = 15.6, 8.0 Hz, 1H), 4.93 (m, 1H), 4.65 (m, 2H), 4.13 (m, 3H) AC31 68-70 610.73 8.42 (s, 1H), 7.76 (m, ([M + H]⁺) 1H), 7.61 (m, 2H), 7.39 (m, 4H), 6.54-6.39 (m, 3H), 4.66 (d, J = 6.0 Hz, 2H), 4.12 (m, 1H) AC32 78-80 555.89 7.61 (m, 2H), 7.40 (m, ([M − H]⁻) 3H), 6.54 (m, 2H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 5.46 (m, 1H), 4.14 (m, 1H), 3.50 (m, 4H) AC33 182- 587.68 7.62 (s, 1H), 7.58 (d, J = 184 ([M − H]⁻) 8.0 Hz, 1H), 7.40 (m, 3H), 6.84 (br s, 1H), 6.55 (d, J = 15.6 Hz, 1H), 6.45 (dd, J = 15.6, 7.6 Hz, 1H), 4.93 (m 1H), 4.65 (m, 2H), 4.13 (m, 4H) AC34 151- 545.83 7.67 (s, 1H), 7.61 (d, J = 153 ([M − H]⁻) 6.0 Hz, 1H), 7.53 (m, 1H), 7.41 (s, 2H), 6.64 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 6.18 (br s, 1H), 5.44 (m, 1H), 4.14 (m, 1H), 3.50 (m, 2H), 3.40 (m, 2H) AC35 100- 577.71 7.70 (s, 1H), 7.63 (m, 3257, 1655, 102 ([M − H]⁻) 1H), 7.53 (d, J = 7.6 Hz, 1113, 808 1H), 7.41 (s, 2H), 6.53 (d, J = 16.0 Hz, 1H), 6.49 (m, 2H), 4.93 (m, 1H), 4.64 (m, 2H), 4.13 (m, 1H), 4.03 (m, 2H) AC36 81-83 600.83 8.40 (s, 1H), 7.73 (m, ([M + H]⁺) 2H), 7.61 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 8.0 Hz, 1H), 7.40 (s, 2H), 7.35 (d, J = 8.0 Hz, 1H), 6.63 (d, J = 16.0 Hz, 1H), 6.46 (dd, J = 16.0, 7.6 Hz, 1H), 6.14 (m, 1H), 4.63 (d, J = 6.0 Hz, 2H), 4.14 (m, 1H) AC37 512.68 8.39 (s, 1H), 7.73 (m, 3268, 1644, ([M + H]⁺) 1H), 7.48 (m, 2H), 7.34 1109, 820 (d, J = 7.6 Hz, 1H), 7.24 (m, 3H), 6.55 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 7.6 Hz, 1H), 6.12 (m, 1H), 4.62 (d, J = 6.0 Hz, 2H), 4.13 (m, 1H), 2.45 (s, 3H) AC38 79-80 528.85 8.46 (m, 1H), 7.73 (m, ([M − H]⁻) 1H), 7.35 (m, 4H), 7.22 (m, 2H), 6.56 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 8.0 Hz, 1H), 4.62 (d, J = 6.0 Hz, 2H), 4.10 (m, 1H), 2.45 (s, 3H) AC39 141- 477.83 9.19 (s, 1H), 8.79 (s, 144 ([M − H]⁻) 2H), 7.37 (m, 2H), 7.23 (m, 2H), 7.21 (m, 1H), 6.57 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 7.6 Hz 1H), 6.21 (m, 1H), 4.65 (s, 2H), 4.11 (m, 1H), 2.46 (s, 3H) AC40 69-72 484.67 8.33 (t, J = 5.6 Hz, 1H), ([M + H]⁺) 8.61 (m, 1H), 7.68 (m, 3H), 7.48 (m, 2H), 6.86 (dd, J = 15.6, 8.2 Hz 1H), 6.74 (d, J = 15.6 Hz, 1H), 4.44 (m, 1H), 3.76 (d, J = 6.0 Hz, 2H), 2.54 (m, 1H), 2.67 (s, 3H), 0.59 (m, 2H), 0.54 (m, 2H) AC41 196- 515.00 8.66 (d, J = 7.6 Hz, 1H), 199 ([M − H]⁻) 8.39 (t, J = 5.6 Hz, 1H), 7.65 (s, 3H), 7.45 (m, 3H), 6.86 (dd, J = 15.6, 8.8 Hz, 1H), 6.74 (d, J = 15.6 Hz, 1H), 5.01 (m, 1H), 4.99 (m, 1H), 3.78 (d, J = 6.0 Hz, 2H), 3.40 (m, 2H), 3.22 (m, 2H), 2.37 (m, 3H) AC42 79-82 534.72 7.99 (d, J = 8.0 Hz, ([M + H]⁺) 1H), 7.89 (d, J = 8.0 Hz, 1H), 7.51 (m, 2H), 7.44 (m, 2H), 7.27 (m, 4H), 6.71 (t, J = 5.2 Hz, 1H), 6.59 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 8.0 Hz, 1H), 5.05 (d, J = 1.6 Hz, 2H), 4.12 (m, 1H), 2.52 (m, 3H) AC43 481.75 8.69 (s, 1H), 8.52 (s, 1663, 1608, ([M + H]⁺) 2H), 7.45 (d, J = 7.6 Hz, 1168, 1114, 1H), 7.37 (d, J = 2.0 Hz, 801 1H), 7.26 (m, 2H), 7.21 (m, 1H), 6.83 (s, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.4 Hz, 1H), 4.81 (d, J = 5.6 Hz, 2H), 4.12 (t, J = 8.4 Hz 1H), 2.45 (s, 3H) AC44 528.01 8.44 (d, J = 2.4 Hz, 1H), 1640, 1166, ([M + H]⁺) 7.69 (d, J = 2.4 Hz, 1H), 1112, 800 7.37 (m, 1H), 7.33 (s, 1H), 7.31 (s, 1H), 7.26 (m, 1H), 7.24 (m, 3H), 6.57 (d, J = 16.0 Hz, 1H), 6.39 (dd, J = 16.0, 8.0 Hz, 1H), 5.96 (d, J = 7.2 Hz, 1H), 5.32 (t, J = 7.2 Hz, 1H), 4.11 (t, J = 8.4 Hz, 1H), 2.41 (s, 3H), 1.61 (d, J = 7.2 Hz, 3H) AC45 512.88 7.66 (s, 1H), 7.37 (d, J = 1657, 1167, ([M + H]⁺) 6.8 Hz, 2H), 7.26 (m, 1106, 800 3H), 7.18 (m, 1H), 7.11 (m, 2H), 6.99 (m, 1H), 6.57 (d, J = 15.6 Hz, 1H), 6.39 (dd, J = 15.6, 8.0 Hz, 1H), 4.11 (t, J = 8.4 Hz, 1H), 3.36 (s, 3H), 2.43 (s, 3H) AC46 61-64 575.93 8.42 (d, J = 2.0 Hz, 1H), ([M + H]⁺) 7.76 (d, J = 2.4 Hz, 1H), 7.61 (m, 2H), 7.39 (m, 3H), 7.26 (s, 2H), 6.54 (d, J = 16.0 Hz, 1H), 6.42 (dd, J = 16.0, 7.6 Hz, 1H), 4.65 (d, J = 6.0 Hz, 2H), 4.14 (m, 1H) AC47 525.89 10.02 (s, 1H), 9.87 (s, 3280, 1640 ([M − H]⁻) 1H), 8.47 (t, J = 6.0 Hz, 1H), 7.66 (s, 3H), 7.44 (s, 1H), 7.40 (d, J = 3.6 Hz, 2H), 6.86 (dd, J = 15.6, 9.2 Hz, 1H), 6.74 (d, J = 15.6 Hz, 1H), 4.82 (t, J = 9.6 Hz, 2H), 3.88 (d, J = 6.0 Hz, 2H), 2.36 (s, 3H), 1.63 (m, 1H), 0.76 (m, 4H) AC48 509.96 7.37 (m, 7H), 7.34 (m, 3275, 1642 ([M − H]⁻) 3H), , 6.57 (d, J = 16.0 Hz, 1H), 6.39 (dd, J = 16.0, 8.0 Hz, 1H), 6.01 (m, 1H), 4.60 (d, J = 6.0 Hz, 2H), 4.13 (m, 1H), 2.46 (s, 3H) AC49 518.85 8.39 (d, J = 2.0 Hz, 1H), 1658, 1112, ([M + H]⁺) 8.11 (m, 1H), 7.71 (d, 1025, 2219 J = 2.4 Hz, 1H), 7.41 (m, 3H), 7.17 (m, 3H), 6.59 (d, J = 16.0 Hz, 1H), 6.47 (dd, J = 16.0, 8.0 Hz, 1H), 4.66 (d, J = 5.6 Hz, 2H), 4.14 (m, 1H) AC50 481.88 8.72 (m, 1H), 7.67 (s, 1654, 1112, ([M + H]⁺) 3H), 7.46 (s, 1H), 7.40 800, 3069 (m, 2H), 7.08 (s, 1H), 6.82 (m, 2H), 6.55 (d, J = 7.6 Hz, 1H), 4.82 (m, 1H), 4.48 (s, 2H), 3.65 (s, 3H), 2.38 (s, 3H) AC51 540.83 7.45 (d, J = 7.6 Hz, 1H), 1652, 1571, ([M + H]⁺) 7.38 (m, 1H), 7.27 (m, 802, 1114, 2H), 7.22 (m, 2H), 6.85 2926 (m, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 4.33 (m, 2H), 4.14 (m, 3H), 3.18 (s, 3H), 2.48 (s, 3H) AC52 488.29 7.33 (m, 2H), 7.25 (m, 1635, 11134, ([M − H]⁻) 3H), 6.56 (d, J = 15.6 813, 2927 Hz, 1H), 6.37 (dd, J = 15.6, 8.0 Hz, 1H), 5.61 (d, J = 8.0 Hz, 1H), 4.21 (m, 1H), 4.01 (m, 1H), 4.08 (m, 2H), 3.56 (t, J = 10.0 Hz, 2H), 2.48 (m, 2H), 2.08 (m, 2H), 1.5 (m, 3H) AC53 532.92 8.49 (d, J = 2.0 Hz, 1H), 1651, 3027, ([M + H]⁺) 7.69 (d, J = 2.4 Hz, 1H), 815, 1113 7.43 (d, J = 8.0 Hz, 1H), 7.34 (m, 3H), 7.26 (m, 2H), 6.95 (m, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 8.0 Hz, 1H), 4.72 (d, J = 5.2 Hz, 2H), 4.09 (m, 1H), 2.47 (s, 3H) AC54 529.06 8.37 (d, J = 5.2 Hz, 1H), 1654, 3434, ([M − H]⁻) 7.41 (d, J = 8.0 Hz, 1H), 814, 1112 7.36 (m, 3H), 7.31 (m, 1H), 7.26 (m, 2H), 6.58 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 7.6 Hz, 1H), 5.20 (t, J = 5.6 Hz, 1H), 4.63 (d, J = 6.0 Hz, 2H), 4.13 (m, 1H), 2.18 (s, 3H) AC57 464.96 8.69 (t, J = 6.0 Hz, 1H), 3417, 1658, ([M + H]⁺) 8.58 (t, J = 6.0 Hz, 1H), 1165, 817 7.92 (s, 1H), 7.87 (d, J = 6.4 Hz, 2H), 7.62 (d, J = 8.4 Hz, 1H), 7.45 (d, J = 8.4 Hz, 1H), 7.0 (m, 1H), 6.76 (d, J = 15.6 Hz, 1H), 6.76 (dd, J = 15.6, 8.0 Hz, 1H), 4.01 (m, J = 8.0 Hz, 1H), 3.71 (m, 2H), 3.49 (m, 2H) AC58 124.4- 599.76 7.62 (m, 2H), 7.40 (s, 126.9 ([M + H]⁺) 2H), 7.37 (d, J = 1.6 Hz, 1H), 6.61 (t, J = 4.8 Hz, 1H), 6.55 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 7.6 Hz, 1H), 4.16 (d, J = 6.0 Hz, 2H), 4.01 (m, 1H), 1.56 (s, 9H) AC59 80-83 497.40 8.42 (d, J = 2.1 Hz, 1H), ([M − H]⁻) 8.29 (d, J = 7.5 Hz, 1H), 7.51 (m, 2H), 7.39 (m, 1H), 7.36 (m, 4H), 7.28 (m, 1H), 6.61 (d, J = 15.9 Hz, 1H), 6.45 (dd, J = 15.9, 7.8 Hz 1H), 4.14 (t, J = 8.4 Hz, 1H), 2.51 (s, 3H) AC60 515.09 8.52 (s, 1H), 8.39 (d, J = 1668, 1589, ([M + H]⁻) 1.8 Hz, 2H), 7.70 (d, J = 1167, 1113, 2.1 Hz, 1H), 7.62 (s, 802 1H), 7.43 (s, 1H), 7.35 (m, 3H), 6.62 (d, J = 16.2 Hz, 1H), 6.52 (dd, J = 16.2, 7.5 Hz, 1H), 4.62 (d, J = 6.3 Hz, 2H), 4.19 (m, 1H), 2.76 (s, 3H) AC61 461.90 8.07 (t, J = 8.0 Hz, 1H), 1658, 1114, ([M − H]⁻) 7.39 (t, J = 2.0 Hz, 1H), 801 7.28 (d, J = 1.2 Hz, 3H), 7.17 (d, J = 1.6 Hz, 1H), 7.11 (m, 1H), 6.59 (d, J = 15.6 Hz, 1H), 6.47 (dd, J = 15.6, 7.6 Hz, 1H), 5.49 (m, 1H), 4.14 (t, J = 8.4 Hz, 1H), 3.48 (m, 4H) AC62 105- 528.88 8.62 (t, J = 6.4 Hz, 1H), 108 ([M − H]⁻) 8.46 (m, 1H), 7.73 (m, 5H), 7.48 (d, J = 7.6 Hz, 1H), 7.03 (dd, J = 15.6, 9.2 Hz, 1H), 6.81 (d, J = 15.6 Hz, 1H), 4.86 (m, 1H), 3.97 (m, 4H) AC63 77-80 594.67 8.43 (s, 1H), 7.76 (d, J = 3257, 1653 ([M + H]⁺) 2.4 Hz, 1H), 7.60 (m, 2H), 7.38 (d, J = 7.6 Hz, 1H), 7.33 (d, J = 6.4 Hz, 3H), 6.54 (d, J = 16.0 Hz, 1H), 6.46 (m, 1H), 6.41 (dd, J = 16.0 8.0 Hz, 1H), 4.65 (d, J = 6.0 Hz, 2H), 4.15 (m, 1H) AC64 83-85 580.72 7.72 (d, J = 8.0 Hz, 1H), ([M − H]⁻) 7.44 (s, 1H), 7.40 (s, 2H), 7.36 (d, J = 6.8 Hz, 1H), 7.05 (t, J = 5.2 Hz, 1H), 6.70 (t, J = 5.2 Hz, 1H), 6.57 (d, J = 15.6 Hz, 1H), 6.44 (dd, J = 15.6, 8.0 Hz, 1H), 4.23 (d, J = 5.6 Hz, 2H), 4.15 (m, 1H), 4.01 (m, 2H) AC65 534.72 8.39 (d, J = 2.0 Hz, 1H), 1658, 1113, ([M − H]⁻) 8.12 (t, J = 8.4 Hz, 1H), 817, 2925 7.71 (d, J = 2.4 Hz, 1H), 7.34 (m, 3H), 7.26 (m, 1H), 7.11 (m, 2H), 6.59 (d, J = 16.0 Hz, 1H), 6.46 (dd, J = 16.0, 8.0 Hz, 1H), 4.66 (d, J = 5.2 Hz, 2H), 4.13 (m, 1H) AC66 73-75 624.61 7.88 (s, 1H), 7.63 (d, J = ([M − H]⁻) 1.6 Hz, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.40 (m, 2H), 6.80 (t, J = 5.6 Hz, 1H), 6.70 (t, J = 5.6 Hz, 1H), 6.56 (d, J = 16.0 Hz, 1H), 6.44 (dd, J = 16.0, 8.0 Hz, 1H), 4.22 (m, 2H), 4.12 (m, 1H), 4.01 (m, 2H) AC67 479.82 8.07 (t, J = 8.0 Hz, 1H), 3272, 1644 ([M − H]⁻) 7.34 (d, J = 6.0 Hz, 2H), 7.28 (s, 1H), 7.17(s, 2H), 6.59 (d, J = 15.6 Hz, 1H), 6.46 (dd, J = 15.6, 8.0 Hz, 1H), 5.49 (m, 1H), , 4.12 (m, 1H), 3.49 (m, 4H). AC68 90-93 546.80 8.6 (t, J = 6.4 Hz, 1H), 3315, 1684 ([M − H]⁻) 8.45 (m, 1H), 7.86 (d, J = 6.4 Hz, 2H), 7.75 (t, J = 8.0 Hz, 1H), 7.63 (d, J = 12.0 Hz, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.03 (dd, J = 15.6, 9.6 Hz, 1H), 6.80 (d, J = 15.6 Hz, 1H), 4.88 (m, 1H), 3.96 (m, 4H) AC69 542.82 7.41 (d, J = 8.0 Hz, 1H), 3294, 1685 ([M − H]⁻) 7.34 (d, J = 5.6 Hz, 2H), 7.26 (m, 1H), 7.23 (m, 1H), 6.81 (s, 1H), 6.57 (d, J = 15.6 Hz, 1H), 6.55 (s, 1H), 6.39 (dd, J = 15.6, 8.0 Hz, 1H), 4.18 (m, 2H), 4.13 (m, 1H), 3.97 (m, 2H), 2.46 (s, 3H) AC70 176- 545.23 8.38 (d, J = 2.4 Hz, 1H), 178 ([M − H]⁻) 8.22 (d, J = 6.8 Hz, 2H), 7.71 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 6.0 Hz, 2H), 7.30 (d, J = 7.6 Hz, 1H), 7.15 (d, J = 1.6 Hz, 1H), 6.93 (d, J = 1.2 Hz, 1H), 6.60 (d, J = 15.6 Hz, 1H), 6.43 (dd, J = 15.6, 7.6 Hz, 1H), 4.66 (d, J = 6.0 Hz, 2H), 4.13 (m, 1H), 3.98 (s, 3H) AC71 492.20 8.24 (d, J = 7.6 Hz, 1H), 1639, 3079, ([M − H]⁻) 8.15 (d, J = 8.4 Hz, 1H), 858 7.35 (d, J = 6.0 Hz, 2H), 7.13 (d, J = 1.2 Hz, 1H), 6.92 (s, 1H), 6.61 (d, J = 16.0 Hz, 1H), 6.43 (dd, J = 16.0, 7.6 Hz, 1H), 5.48 (m, 1H), 4.13 (m, 1H), 4.03 (s, 3H), 3.48 (m, 4H) AC72 543.05 8.42 (d, J = 2.4 Hz, 1H), 1642, 3246, ([M − H]⁻) 7.75 (d, J = 2.4 Hz, 1H), 814, 1113 7.34 (m, 4H), 7.20 (m, 2H), 6.60 (d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0, 8.0 Hz, 1H), 6.12 (t, J = 5.6 Hz, 1H), 4.62 (d, J = 6.0 Hz, 2H), 4.20 (m, 1H), 2.82 (m, 2H), 1.45 (t, J = 5.6 Hz, 3H) AC75 644.78 8.72 (s, 1H), 7.97 (d, J = 3431, 1652, ([M + H]⁺) 7.2 Hz, 1H), 7.70 (d, J = 1171, 809 8.4 Hz, 1H), 7.61 (m, 2H), 7.40 (m, 2H), 6.55 (m, 2H), 6.42 (dd, J = 16.0, 8.0 Hz, 1H), 4.76 (d, J = 6.0 Hz, 2H), 4.12 (m, 1H) AC76 531.34 8.87 (t, J = 6.0 Hz, 1H), 3120, 1708, ([M + H]⁺) 8.34 (d, J = 2.1 Hz, 1H), 1171 7.85 (d, J = 6.3 Hz, 3H), 7.48 (m, 4H), 6.57 (d, J = 15.6 Hz, 1H), 6.45 (dd, J = 15.6, 9.0 Hz, 1H), 4.84 (m, 1H), 4.49 (d, J = 5.7 Hz, 2H), 2.82 (m, 2H), 2.36 (t, J = 5.6 Hz, 3H) AC77 531.1 8.87 (t, J = 6.0 Hz, 1H), 3444, 1648, ([M + H]⁺) 8.34 (d, J = 2.1 Hz, 1H), 1114, 814 7.85 (d, J = 6.3 Hz, 3H), 7.48 (m, 4H), 6.57 (d, J = 15.6 Hz, 1H), 6.45 (dd, J = 15.6, 8.0 Hz, 1H), 4.84 (m, 1H), 4.49 (d, J = 5.7 Hz, 2H), 2.36 (s, 3H) AC78 561.06 8.59 (t, J = 6.4 Hz, 1H), 3432, 1631, ([M + H]⁺) 8.47 (t, J = 5.6 Hz, 1H), 1161, 840 7.89 (s, 2H), 7.45 (m, 3H), 6.87 (m, 1H), 6.75 (d, J = 15.6 Hz, 1H), 4.85 (t, J = 8.0 Hz 1H), 3.98 (m, 4H), 2.58 (s, 3H) AC79 610.97 8.69 (t, J = 6.0 Hz, 1H), 3303, 1658, ([M + H]⁺) 8.58 (t, J = 6.0 Hz, 1H), 1166, 817 7.92 (s, 1H), 7.87 (d, J = 6.4 Hz, 2H), 7.62 (d, J = 8.4 Hz, 1H), 7.45 (d, J = 8.4 Hz, 1H), 7.0 (m, 1H), 6.76 (d, J = 15.6 Hz, 1H) 4.83 (t, J = 8.0 Hz, 1H), 3.98 (m, 4H) AC80 561.06 7.37 (m, 3H), 7.26 (m, 3412, 1624, ([M + H]⁺) 1H), 7.24 (m, 1H), 6.59 1157, 825 (d, J = 15.6 Hz, 1H), 6.39 (dd, J = 15.6, 8.0 Hz, 1H), 4.24 (m, 4H), 3.90 (m, 1H), 2.83 (m, 2H), 1.26 (m, 3H) AC81 9-92 546.93 8.73 (d, J = 5.6 Hz, 1H), ([M − H]⁻) 8.45 (t, J = 6.0 Hz, 1H), 7.76 (s, 3H), 7.45 (m, 3H), 6.86 (dd, J = 16.0, 9.2 Hz, 1H), 4.83 (m, 1H), 4.56 (m, 2H), 4.51 (m, 1H), 4.10 (m, 2H), 3.85 (d, J = 6.0 Hz, 2H), 2.50 (m, 3H) AC82 477.69 7.38 (d, J = 1.8 Hz, 2H), 1646, 1353, ([M + H]⁺) 7.33 (s, 1H), 7.27 (s, 3H), 1196, 1112, 6.58 (d, J = 16.0 800 Hz, 1H), 6.42 (d, J = 8.1 Hz, 1H), 6.36 (dd, J = 16.0, 7.8 Hz, 1H), 4.71 (m, 1H), 4.23 (m, 3H), 3.26 (m, 2H), 2.45 (s, 3H) AC83 493.83 8.07 (t, J = 8.4 Hz, 1H), 1527, 1113, ([M − H]⁻) 7.39 (t, J = 1.6 Hz, 1H), 801, 1167, 7.31 (d, J = 1.2 Hz, 1H), 1321 7.26 (m, 2H), 7.23 (m, 1H), 7.19 (d, J = 1.6 Hz, 1H), 6.60 (d, J = 16.8 Hz, 1H), 6.49 (dd, J = 16.8, 7.6 Hz, 1H), 4.90 (m, 1H), 4.64 (m, 2H), 4.14 (m, 2H), 4.10 (m, 1H) AC84 511.75 8.07 (t, J = 8.0 Hz, 1H), 1645, 1113, ([M − H]⁻) 7.34 (m, 3H), 7.19 (d, J = 804, 3030, 13.2 Hz, 1H), 6.60 (d, J = 1245 16.4 Hz, 1H), 6.48 (dd, J = 16.4, 8.0 Hz, 1H), 4.88 (m, 1H), 4.62 (m, 2H), 4.12 (m, 3H) AC85 523.83 8.60 (d, J = 6.8 Hz, 1H), 1652, 3039, ([M − H]⁻) 8.15 (d, J = 8.4 Hz, 1H), 802, 1114 7.35 (d, J = 6.0 Hz, 1H), 7.15 (d, J = 7.2 Hz, 1H), 6.94 (s, 1H), 6.60 (d, J = 15.6 Hz, 1H), 6.44 (dd, J = 7.6, 7.6 Hz, 1H), 4.93 (m, 1H), 4.62 (m, 2H), 4.13 (m, 6H) AC86 524.36 7.35 (d, J = 6.3 Hz, 3H), 3333, 1651, ([M + H]⁺) 7.26 (m, 2H), 7.20 (m, 815 1H), 6.60 (d, J = 15.9 Hz, 1H), 6.47 (dd, J = 15.9, 6.6 Hz, 1H), 4.86 (m, 1H), 4.65 (m, 2H), 4.13 (m, 3H), 2.84 (q, 2.8 Hz, 2H), 1.26 (m, 3H) AC87 495.82 8.07 (t, J = 8.0 Hz, 1H), 1623, 1114, ([M − H]⁻) 7.52 (m, 3H), 7.19 (d, 816 J = 13.2 Hz, 1H), 6.59 (d, J = 16.4 Hz, 1H), 6.47 (dd, J = 16.4, 8.0 Hz, 1H), 4.69 (m, 1H), 4.23 (m, 3H), 3.29 (m, 2H) AC89 509.89 7.43 (m, 2H), 7.27 (m, 1666, 1166, ([M + H]⁺) 2H), 7.23 (m, 2H), 6.58 1112, 800 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 7.6 Hz, 1H), 4.79 (d, J = 5.6 Hz, 2H), 4.14 (m, 1H), 2.48 (s, 3H), 2.18 (m, 1H), 1.16 (m, 4H) AC90 656.9 8.34 (m, 1H), 8.27 (m, ([M − H]⁻) 1H), 7.60 (d, J = 1.6 Hz, 1H), 7.49 (d, J = 8.0 Hz, 2H), 7.40 (s, 2H), 7.36 (dd, J = 8.2, 1.7 Hz, 1H), 6.53 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 15.9, 7.9 Hz, 1H), 4.89 (d, J = 8.4 Hz, 2H), 4.48 (d, J = 9.0 Hz, 2H), 4.11 (m, 1H) AC91 640.9 8.18 (t, J = 5.0 Hz, 1H), ([M − H]⁻) 7.58 (d, J = 1.6 Hz, 1H), 7.47 (d, J = 8.0 Hz, 1H), 7.40 (s, 2H), 7.34 (dd, J = 8.1, 1.6 Hz, 1H), 6.52 (m, 2H), 6.37 (dd, J = 15.9, 7.9 Hz, 1H), 4.54 (d, J = 4.9 Hz, 2H), 4.12 (m, 1H), 3.99 (qd, J = 8.9, 6.5 Hz, 2H) AC92 640.9 9.16 (d, J = 6.1 Hz, 1H), ([M − H]⁻) 7.65 (d, J = 1.6 Hz, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.41 (m, 3H), 7.21 (t, J = 5.6 Hz, 1H), 6.55 (d, J = 15.9 Hz, 1H), 6.41 (dd, J = 15.9, 7.8 Hz, 1H), 4.59 (d, J = 5.6 Hz, 2H), 4.45 (qd, J = 9.0, 6.0 Hz, 2H), 4.12 (q, J = 7.2 Hz, 1H) AC93 485.5 7.52-7.41 (d, J = 8.2 Hz, ¹C NMR (δ)³ ([M + H]⁺) 1H), 7.39-7.34 (m, 1H), 169.91, 169.84, 7.24-7.17 (d, J = 1.8 Hz, 138.23, 137.41, 2H), 7.02-6.92 (m, 2H), 136.84, 134.79, 6.90-6.83 (d, J = 11.4 134.69, 131.07, Hz, 1H), 6.71 (br s, 1H), 128.69, 127.49, 6.17 (br s, 1H), 6.12- 127.43, 126.72, 6.01 (dd, J = 11.4, 10.3 126.61 (q, J = Hz, 1H), 4.44-4.38 (d, 212.10 Hz), J = 4.2 Hz, 1H), 4.35-4.27 125.61, (m, 1H), 4.10-3.99 (d, J = 123.76, 47.89 5.1 Hz, 2H), 2.78-2.67 (q, J = 28.28 (m, 1H), 2.44 (s, 3H), Hz), 43.46, 0.88-0.78 (m, 2H), 0.60- 22.65, 19.97, 0.45 (m, 2H) 8.21 AC94 511.6 8.36-8.24 (d, J = 2.4 3262, 1607, ([M]-) Hz, 1H), 7.75-7.64 (m, 1247, 1164, 1H), 7.38-7.24 (m, 3H), 1111 7.24-7.09 (d, J = 1.8 Hz, 2H), 6.99-6.90 (m, 2H), 6.89-6.74 (d, J = 11.4 Hz, 1H), 6.63- 6.43 (m, 1H), 6.14- 5.98 (m, 1H), 4.69- 4.51 (d, J = 6.1 Hz, 2H), 4.37-4.20 (m, 1H), 2.46-2.31 (s, 3H) AC95 48-61 626.9 7.58 (d, J = 7.9 Hz, 1H), ([M + H]⁺) 7.44-7.29 (m, 3H), 7.14 (dd, J = 7.9, 1.6 Hz, 1H), 6.86 (d, J = 11.4 Hz, 1H), 6.76 (t, J = 5.9 Hz, 1H), 6.59 (br s, 1H), 6.21-6.04 (m, 1H), 4.23 (d, J = 5.5 Hz, 1H), 3.98 (qd, J = 9.0, 6.5 Hz, 2H) AC96 619.6 8.83 (s, 1H), 8.06 (br, 1616, 1114 ([M + H]⁺) 1H), 7.90 (s, 2H), 7.63 (d, J = 8.1 Hz, 2H), 7.53 (m, 1H), 6.94 (m, 1H), 6.77 (d, J = 15.3 Hz, 1H), 6.63 (d, J = 9.3 Hz, 1H), 4.84 (m, 1H), 4.30 (d, J = 5.6 Hz, 2H), 2.99 (s, 6H) AC97 606.6 8.20 (d, J = 2.1 Hz, 1H), 1644, 1113 ([M + H]⁺) 7.73 (d, J = 2.7 Hz, 1H), 7.60 (m, 2H), 7.39 (s, 2H), 7.29 (m, 1H), 6.79 (d, J = 8.4 Hz, 1H), 6.55 (d, J = 15.9 Hz, 1H), 6.40 (m, 2H), 4.60 (d, J = 2.7 Hz, 2H), 4.13 (m, 1H), 3.95 (s, 3H) AC98 577.87 9.04 (t, J = 6.0 Hz, 1H), 1663, 1168 ([M + H]⁺) 8.60 (t, J = 6.6 Hz, 1H), 8.25 (s, 1H), 7.97 (d, J = 8.1 Hz, 1H), 7.87 (d, J = 6.3 Hz, 2H), 7.69 (d, J = 7.5 Hz, 1H), 7.15 (dd, J = 15.9, 9.3 Hz, 1H), 6.89 (d, J = 15.9 Hz, 1H), 4.86 (m, 1H), 3.98 (m, 4H). AC99 574.81 8.69 (t, J = 6.0 Hz, 1H), 1650, 1164 ([M + H]⁺) 8.58 (t, J = 6.6 Hz, 1H), 7.91 (s, 1H), 7.85 (m, 1H), 7.61 (m, 2H), 7.52 (m, 2H), 6.98 (dd, J = 15.3, 9.0 Hz, 1H), 6.76 (d, J = 15.3 Hz, 1H), 4.81 (m, 1H), 4.01 (m, 4H) AC100 673.80 8.29 (s, 1H), 8.22 (d, J = 3403, 1659 ([M + H]⁺) 8.1 Hz, 1H), 7.93 (d, J = 7.8 Hz, 1H), 7.72 (m, 1H), 7.65 (m, 2H), 7.40 (s, 2H), 7.18 (br, 1H), 6.59 (d, J = 16.0 Hz, 1H), 6.43 (dd, J = 16.0, 7.6 Hz, 1H), 5.02 (d, J = 1.2 Hz, 2H), 4.12 (m, 1H) AC101 636.83 7.56 (d, J = 9.0 Hz, 1H), 1637, 1113 ([M + H]⁺) 7.39 (d, J = 6.0 Hz, 2H), 7.26 (m, 2H), 6.54 (d, J = 15.9 Hz, 1H), 6.37 (dd, J = 8.0, 15.9 Hz, 1H), 4.01 (m, 1H), 3.84 (m, 2H), 3.33 (m, 2H), 3.04 (m, 2H), 2.84 (m, 3H), 2.62 (m, 1H) AC102 592.84 7.60 (m, 2H), 7.32 (m, 1H), 1668, 1167 ([M + H]⁺) 7.03 (d, J = 7.2 Hz, 2H), 6.74 (br, 1H), 6.62 (br, 1H), 6.56 (d, J = 16.2 Hz, 1H), 6.41 (dd, J = 16.2, 7.8 Hz, 1H), 4.22 (d, J = 5.4 Hz, 2H), 4.14 (m, 1H), 4.01 (m, 2H) AC103 99.2- 612.7 8.40 (d, J = 8.0 Hz, 1H), 1634, 1113, 105.0 ([M + H]⁺) 7.92 (d, J = 5.2 Hz, 1H), 809 7.59 (d, J = 8.0 Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H), 6.99 (dd, J = 16.0, 7.6 Hz, 1H), 6.76 (d, J = 16.0 Hz, 1H), 4.84 (m, 1H), 4.23 (d, J = 13.2 Hz, 1H), 3.97 (m, 1H), 3.79 (d, J = 13.6 Hz, 1H), 3.16 (t, J = 11.2 Hz, 1H), 2.77 (t, J = 11.2 Hz, 1H), 1.99 (s, 3H), 1.88 (m, 2H), 1.45 (m, 2H) AC104 680.97 7.60 (m, 2H), 7.40 (m 3437, 1644, ([M + H]⁺) 3H), 6.55 (d, J = 15.6 1113, 807, Hz, 1H), 6.41 (dd, J = 511 15.6, 7.8 Hz, 1H), 4.24 (m, 1H), 3.34 (m, 2H), 2.90 (m, 1H), 2.24 (m, 2H), 1.52(m, 2H), 1.34 (m, 4H) AC105 609.9 7.59 (s, 1H), 7.55 (m, 3303, 1649, ([M + H]⁺) 1H), 7.50 (m, 1H), 7.40 1115, 2242, (m, 2H), 6.54(d, J = 809, 506 16.0 Hz, 1H), 6.50 (J = 16.0, 8.0 Hz, 1H), 4.14 (m, 2H), 3.08 (m, 4H), 2.67 (m, 2H), 2.12 (m, 2H), 1.70 (m, 2H). AC106 584.95 7.59 (s, 1H), 7.51 (d, J = 3417, 1648, ([M + H]⁺) 8.4 Hz, 1H), 7.40 (s, 2H), 1112, 805, 7.36 (d, J = 6.8 Hz, 1H), 555 6.54 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 6.03 (d, J = 8.0 Hz, 1H), 4.11 (m, 2H), 3.10 (m, 2H), 2.50 (m, 2H ), 2.50 (s, 3H) (m, 2H), 1.94 (m, 2H) AC107 609.9 8.41 (d, J = 7.8 Hz, 1H), 3303, 1645, ([M + H]⁺) 7.90 (s, 2H), 7.62 (m, 1115, 2243, 2H), 7.51(m, 1H), 6.92 810, 507 (dd, J = 15.9, 9.0 Hz, 1H), 6.77 (d, J = 15.9 Hz, 1H), 4.81 (m, 1H), 3.73 (s, 2H), 3.31 (m, 1H), 3.28 (m, 1H), 2.82 (t, J = 11.4 Hz, 2H), 2.82 (m, 2H), 2.30 (m, 2H), 1.88 (m, 2H), 1.57 (m, 2H) AC108 626.9 7.60 (m, 2H) 7.39 (s, 3420, 1649, ([M + H]⁺) 2H), 7.28 (m, 1H), 6.56 1113, 809, (d, J = 15.6 Hz, 1H), 554 6.40 (dd, J = 15.6, 7.8 Hz, 1H), 5.91 (m, 1H), 4.65 (m, 2H), 4.10 (m, 1H), 4.07 (m, 2H), 3.59 (m, 1H), 2.74 (m, 2H), 2.13 (m, 4H), 2.07 (m, 1H) AC109 614.6 7.56 (m, 2H), 7.39 (s, 1647, 1113 ([M + H]⁺) 2H), 7.29 (s, 1H), 6.50 (d, J = 15.9 Hz, 1H), 6.41 (dd, J = 15.9, 8.0 Hz 1H), 4.09 (m, 1H), 3.88 (m, 2H), 3.49 (m, 2H), 2.92 (m, 2H), 2.81 (m, 1H), 2.74 (m, 2H), 2.25 (m, 4H) AC110 572.6 11.20 (s, 1H), 8.66 (br, 3412, 1690, ([M + H]⁺) 1H), 7.92 (m, 3H), 7.62 1114, 846, (d, J = 8.0 Hz, 1H), 7.45 559 (d, J = 8.0 Hz, 1H), 6.77 (dd, J = 15.6, 9.2 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.85 (m, 1H), 3.74 (d, J = 5.2 Hz, 2H), 3.61 (s, 3H) AC111 582.79 8.63 (t, J = 6.0 Hz, 1H), 3419, 1659, ([M + H]⁺) 8.04 (t, J = 6.0 Hz, 1H), 843, 557 7.92 (m, 3H), 7.62 (d, J = 1.2 Hz, 1H), 7.47 (d, J = 7.6 Hz, 1H), 7.00 (dd, J = 15.6, 8.8 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 5.19 (d, J = 1.6 Hz, 1H), 5.01 (d, J = 1.2 Hz, 1H), 4.85 (m, 1H), 3.86 (d, J = 5.6 Hz, 2H), 3.75 (t, J = 5.6 Hz, 2H) AC112 582.79 8.84 (br, 1H), 8.58 (m, 3399, 1662, ([M + H]⁺) 1H), 8.30 (m, 1H), 7.91 1114, 807, (s, 2H), 7.61 (d, J = 8.1 582 Hz, 1H), 7.42 (d, J = 7.8 Hz, 1H), 7.00 (dd, J = 15.6, 9.3 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.85 (m, 1H), 4.11 (d, J = 5.6 Hz, 1H), 3.73 (d, J = 5.6 Hz, 1H), 3.04 (s, 6H) AC113 626.88 8.48 (t, J = 5.2 Hz, 1H), 3431, 1651, ([M + H]⁺) 8.3 (s, 1H), 7.90 (s, 2H), 1113, 808, 7.79 (dd, J = 2.0, 2.0 Hz 554 2H), 7.58 (d, J = 8.4 Hz, 1H) 7.46 (d, J = 7.6 Hz, 1H) 7.26 (d, J = 7.6 Hz, 1H), 6.98 (m, 1H), 6.75 (d, J = 15.6 Hz, 1H), 4.85 (m, 1H), 3.49 (d, J = 6.4 Hz, 2H) 2.87 (t, J = 6.4 Hz, 2H) AC114 113.7- 570.7 8.77 (s, 1H), 8.58 (d, J = 117.5 ([M + H]⁺) 7.2 Hz, 2H), 7.93 (d, J = 7.2 Hz, 2H), 7.60 (dd, J = 1.2, 0.8 Hz, 1H), 7.37 (d, J = 7.6 Hz, 1H), 6.99 (m, 1H), 6.77 (d, J = 16 Hz, 1H), 4.85 (m, 1H), 4.10 (m, 1H) 3.29 (m, 2H), 3.05 (m, 2H), 2.0 (m, 2H), 1.76 (m, 2H) AC115 529.00 8.43 (s, 1H), 7.79 (d, J = 1589, 3459, ([M + H]⁺) 8.0 Hz, 1H), 7.51 (m, 1H), 801, 1110 7.36 (d, J = 8.4 Hz, 3H), 7.21 (m, 3H), 6.55 (d, J = 15.6 Hz, 1H), 6.36 (dd, J = 15.6, 8.0 Hz, 1H), 5.04 (d, J = 5.6 Hz, 2H), 4.10 (m, 1H), 2.35 (s, 3H) AC116 614.87 7.99 (d, J = 8.4 Hz, 1H), 3424, 1657, ([M + H]⁺) 7.46 (d, J = 1.6 Hz, 1H), 1165 7.34 (d, J = 6.4 Hz, 2H), 7.28 (m, 2H), 6.62 (m, 2H), 6.47 (dd, J = 16.0, 7.2 Hz, 1H), 4.23 (m, 2H), 4.12 (m, 1H), 4.00 (m, 2H) AC117 525.42 8.39 (br, 1H), 7.85 (br, 3401, 1636, ([M − H]⁻) 1H), 7.62 (m, 3H), 7.53 1113, 750 (d, J = 8.0 Hz, 1H), 7.46 (s, 1H), 7.40 (d, J = 8.0 Hz, 1H), 7.17 (m, 1H), 6.78 (dd, J = 16.0, 8.8 Hz, 1H), 6.70 (m, 1H), 4.77 (m, 1H), 4.66 (s, 1H), 4.32 (s, 1H), 2.97 (s, 3H), 2.16 (s, 3H) AC118 471.79 7.36 (d, J = 8.0 Hz, 2H), 3437, 1655, ([M + H]⁺) 7.27 (m, 2H), 7.22 (m, 1262, 1105, 2H), 6.57 (d, J = 16.0 802 Hz, 1H), 6.38 (dd, J = 16.0, 8.0 Hz, 1H), 6.10 (br, 1H), 4.15 (m, 2H), 3.89 (m, 1H), 3.80 (m, 2H), 3.35 (m, 1H), 2.46 (s, 3H), 2.06 (s, 1H), 1.96 (m, 2H), 1.65 (m, 1H) BC1 492.17 7.39 (s, 2H), 7.25-7.18 3211, 1569, ([M + H]⁺) (m, 3H), 6.58 (d, J = 1113, 806 16.0 Hz, 1H), 6.30 (dd, J = 16.0, 8.4 Hz, 1H), 5.91-5.70 (br, 2H), 4.05 (m, 1H), 3.05- 2.80 (m, 6H), 2.70 (m, 1H), 1.81 (m, 1H) BC2 506.4 8.80 (s, 1H), 8.20 (s, 2923, 1542, ([M + H]⁺) 1H), 7.82 (m, 3H), 7.4 1033, 805 (s, 2H), 6.62 (d, J = 16.0 Hz, 1H), 6.52 (dd, J = 16.0, 8.0 Hz, 1H), 4.18(m, 1H), 3.38 (m, 2H), 2.98 (m, 2H), 2.71 (m, 1H), 2.04 (m, 2H), 1.54 (s, 3H). BC3 518.04 7.40 (s, 2H), 7.33-7.22 3120, 1592, ([M − H]⁻) (m, 3H), 6.61 (d, J = 1146, 895 16.0 Hz, 1H), 6.34- 6.28 (dd, J = 16.0, 8.0 Hz, 1H), 5.96-5.80 (m, 3H), 5.22 (m, 4H), 4.01 (m, 2H), 2.84-2.99 (m, 2H), 2.71 (m, 1H), 1.86 (m, 1H) BC4 529.02 7.39 (s, 2H), 7.25-7.20 3283, 1652, ([M + H]⁺) (m, 3H), 6.34 (d, J = 1241, 811 16.0 Hz, 1H), 6.30 (dd, J = 16.0, 8.0 Hz, 1H), 5.81 (br, 1H), 5.48 (m, 1H), 4.10 (m, 1H), 3.10 (m, 2H), 2.86-3.07 (m, 2H), 2.86 (m, 1H), 1.81 (m, 1H); BC5 544.25 7.40 (s, 2H), 7.21 (s, 3489, 3291, ([M − H]⁻) 1H), 7.12 (m, 1H), 6.56 1655, 1112, (d, J = 16.0 Hz, 1H), 808 6.32 (dd, J = 16.0, 8.4 Hz, 1H), 5.85 (br s, 1H), 5.23 (br s, 1H), 4.12 (m, 1H), 3.18 (m, 3H), 2.80 (m, 3H), 2.08 (m, 2H), 1.83 (m, 5H), 1.25 (m, 2H), 1.01 (m, 3H), 0.78 (m, 2H) BC6 485.96 7.40 (s, 2H), 7.31-7.18 3429, 1114, ([M − H]⁻) (m, 3H), 6.58 (d, J = 804 16.0 Hz, 1H), 6.24- 6.28 (dd, J = 16.0, 8.0 Hz, 1H), 5.40 (br, 1H), 4.01 (m, 2H), 2.78- 3.01 (m, 2H), 2.51 (s, 1H), 1.86 (m, 1H), 1.20 (m, 2H), 1.01 (m, 2H), 0.78 (m, 2H) BC7 500.01 7.40 (s, 2H), 7.31 (s, 1H), 3296, 1115, ([M − H]⁻) 7.18 (m, 1H), 7.18 806 (s, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.32 (dd, J = 16.0, 8.0 Hz, 1H), 5.78 (br s, 1H), 5.21 (br s, 1H), 4.01 (m, 1H), 2.78 (m, 2H), 2.01 (m, 1H), 1.86 (m, 4H), 1.25 (m, 2H), 1.01 (m, 3H), 0.78 (m, 2H) BC8 511.88 7.38-7.20 (m, 5H), 6.62 1657, 1113, ([M − H]⁻) (d, J = 16.0 Hz, 1H), 855 6.34 (dd, J = 16.0, 8.0 Hz, 1H), 5.83 (br, 1H), 5.52 (m, 1H), 4.12 (m, 1H), 3.12 (m, 2H), 3.06- 2.82 (m, 2H), 2.75 (m, 1H), 1.85 (m, 1H) BC9 179- 556.83 8.30 (s, 1H), 7.68 (d, J = 181 ([M − H]⁻) 6.4 Hz, 1H), 7.38-7.20 (m, 5H), 6.60 (d, J = 16.0 Hz, 1H), 6.34 (dd, J = 16.0, 8.0 Hz, 1H), 5.63 (br, 1H), 5.52 (m, 1H), 4.12 (m, 1H), 3.56 (s, 2H), 3.06-2.82 (m, 2H), 2.70 (m, 1H), 1.82 (m, 1H) BC10 497.98 7.38-7.20 (m, 5H), 6.62 3027, 1654, ([M − H]⁻) (d, J = 16.0 Hz, 1H), 815 6.34 (dd, J = 16.0, 8.0 Hz, 1H), 5.83 (br, 1H), 5.52 (m, 1H), 4.12 (m, 1H), 3.02 (m, 3H), 2.82 (m, 1H), 2.50 (m, 3H), 1.82 (m, 1H), 1.42 (m, 1H) BC11 530.09 7.80 (m, 1H), 7.48 (m, 1715, 1113, ([M − H]⁻) 2H), 7.32 6.65 (d, J = 816 16.0 Hz, 1H), 6.54 (dd, J = 16.0, 8.0 Hz, 1H), 5.38 (m, 1H), 4.18 (m, 1H), 3.62 (m, 1H), 3.32 (m, 1H), 2.86 (m, 1H), 1.81 (m, 1H) BC12 514.86 7.32, (d, J = 6.0 Hz, 2H) 3428, 1112, ([M + H]⁺) 7.28 (m, 1H), 7.20 (d, J = 857 8.0, 1H), 7.14 (d, J = 8.8, 1H), 6.70 (d, J = 8.0 Hz, 1H), 6.60 (m, 2H), 4.15 (m, 1H), 3.85 (m, 1H), 3.65 (m, 1H), 3.46 (m, 2H), 3.19 (m, 2H); BC13 121- 553.06 8.33 (br, 1H), 7.59 (s, 126 ([M − H]⁻) 1H), 7.45 (m, 3H), 6.72 (d, J = 3.6, 1H), 6.39 (m, 1H), 4.71 (t, J = 7.2 Hz, 2H), 4.15 (m, 2H) BC14 172- 554.0 8.83 (t, J = 6.6 Hz, 1H), 175 ([M − H]⁻) 8.42 (t, J = 14.7 Hz, 1H), 8.22 (d, J = 8.1 Hz, 1H), 8.13 (t, J = 6.3 Hz, 1H), 7.98-7.86 (m, 2H), 7.16-7.07 (m, 1H), 7.01-6.93 (m, 1H), 4.96-4.81 (m, 3H), 4.00-3.88 (m, 2H) CC1 107- 402.00 7.37 (m, 3H), 7.28 (m, 109 ([M + H]⁺) 4H), 6.60 (d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0, 8.0 Hz, 1H), 5.75 (br s, 1H), 4.46 (d, J = 6 Hz, 2H), 4.01 (m, 1H), 2.11 (s, 3H) CC2 118- 428.11 7.37 (m, 3H), 7.28 (m, 120 ([M + H]⁺) 4H), 6.60 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 5.83 (br s, 1H), 4.46 (d, J = 6.0 Hz, 2H), 4.11 (m, 1H), 1.40 (m, 1H), 1.02 (m, 2H), 0.77 (m, 2H) CC3 119- 468.20 7.38 (m, 3H), 7.27 (m, 122 ([M − H]⁻) 3H), 6.60 (d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0, 8.4 Hz, 1H), 5.00 (br s, 1H), 4.48 (d, J = 5.6 Hz, 2H), 4.11 (m, 1H), 3.15 (q, J = 10.4 Hz, 2H) CC4 414.16 7.37 (m, 3H), 7.28 (m, ([M − H]⁻) 3H), 6.60 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 5.69 (br s, 1H), 4.46 (d, J = 6.0 Hz, 2H), 4.21 (m, 1H), 2.29 (q, J = 5.8 Hz, 2H), 1.30 (t, J = 7.2 Hz, 3H) CC5 460.28 7.40 (m, 3H), 7.28 (m, ([M − H]⁻) 2H), 6.60 (d, J = 15.6 Hz, 1H), 6.33 (dd, J = 15.6, 8.0 Hz, 1H), 5.84 (br s, 1H), 4.46 (d, J = 5.6 Hz, 2H), 4.10 (m, 1H), 1.36 (m, 1H), 1.02 (m, 2H), 0.77 (m, 2H) CC6 106- 504.08 7.40 (m, 3H), 7.26 (m, 108 ([M − H]⁻) 1H), 6.60 (d, J = 16.0 Hz, 1H), 6.34 (dd, J = 16.0, 8.0 Hz, 1H), 5.96 (br s, 1H), 4.49 (d, J = 5.6 Hz, 2H), 4.10 (m, 1H), 3.15 (q, J = 10.8 Hz, 2H) CC7 127- 436.03 7.42 (m, 4H), 7.24 (m, 128 ([M + H]⁺) 2H), 6.53 (d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0, 8.0 Hz, 1H), 5.86 (br s, 1H), 4.51 (d, J = 6.0 Hz, 2H), 4.05 (m, 1H), 2.02 (s, 3H) CC8 129- 462.15 8.58 (t, J = 5.6 Hz, 1H), 131 ([M + H]⁺) 7.72 (m, 1H), 7.66 (m, 3H), 7.49 (d, J = 8.0 Hz, 1H), 7.30 (d, J = 8.0 Hz, 1H), 6.90 (dd, J = 16.0, 8.0 Hz, 1H), 6.73 (d, J = 16 Hz, 1H), 4.81 (m, 1H), 4.33 (d, J = 6.0 Hz, 1H), 1.64 (m, 1H), 0.68 (m, 4H) CC9 132- 504.25 7.41 (m, 3H), 7.26 (m, 134 ([M + H]⁺) 3H), 6.54 (d, J = 16.0 Hz, 1H), 6.37 (dd, J = 16.0, 8.0 Hz, 1H), 6.13 (br s, 1H), 4.56 (d, J = 6.0 Hz, 2H), 4.11 (m, 1H), 3.13 (m, 2H) CC10 538.03 7.38 (m, 4H), 6.56 (d, 1651, 1112, ([M + 2H]⁺) J = 16.0 Hz, 1H), 6.38 807 (dd, J = 16.0, 8.0 Hz, 1H), 6.18 (m, 1H), 4.58 (m, 2H), 4.08 (m, 1H), 3.08 (m, 2H) CC11 111- 494.12 7.42 (m, 3H), 7.24 (m, 112 ([M − H]⁻) 1H), 6.54 (d, J = 15.6 Hz, 1H), 6.34 (dd, J = 16.0, 8.0 Hz, 1H), 6.03 (m, 1H), 4.53 (d, J = 6.0 Hz, 1H), 4.10 (m, 1H), 1.39 (m, 1H), 1.00 (m, 2H), 0.77 (m, 2H) CC12 76-78 510.07 7.39 (s, 4H), 7.34 (d, J = ([M − H]⁻) 8.0 Hz, 1H), 7.26 (m, 1H), 6.57 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 6.10 (br s, 1H), 4.49 (d, J = 6.0 Hz, 2H), 4.10 (m, 1H), 1.20 (s, 9H) CC13 73-76 563.37 8.51 (d, J = 5.2 Hz, 1H), ([M − H]⁻) 7.63 (s, 1H), 7.51 (m, 1H), 7.45 (m, 2H), 7.39 (s, 2H), 7.28 (m, 1H), 6.58 (m, 2H), 6.37 (dd, J = 16.0, 8.0 Hz, 1H), 4.71 (d, J = 6.0 Hz, 1H), 4.11 (m, 1H) CC14 581.45 8.51 (m, 1H), 8.30 (d, 3430, 1656, ([M+1H]⁺) J = 2.4 Hz, 1H), 7.73 (m, 1109, 806 1H), 7.61 (s, 2H), 7.51 (s, 1H), 7.32 (m, 3H), 6.66 (d, J = 16.0 Hz, 1H), 6.56 (dd, J = 16.0, 8.4 Hz, 1H), 4.50 (m, 1H), 4.45 (d, J = 5.6 Hz, 1H), 3.56 (s, 2H) CC15 480.24 7.40 (m, 3H), 7.33 (m, 3293, 1651, ([M + H]⁺) 1H), 7.22 (m, 2H), 6.54 1543, 1114, (d, J = 15.6 Hz, 1H), 812 6.34 (dd, J = 16.0, 8.0 Hz, 1H), 6.03 (br s, 1H), 4.53 (d, J = 6.0 Hz, 2H), 4.13 (m, 1H), 1.41 (m, 1H), 1.00 (m, 2H), 0.77 (m, 2H) CC16 520.33 7.42 (s, 1H), 7.37 (m, 3307, 1665, ([M − H]⁻) 3H), 7.22 (m, 1H), 6.54 1114, 813 (d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0, 8.0 Hz, 1H), 6.19 (br s, 1H), 4.51 (d, J = 6.0 Hz, 2H), 4.21 (m, 1H), 3.33 (m, 2H) CC17 117- 459.83 7.51 (m, 2H), 7.39 (m, 3293, 1633, 119 ([M − H]⁻) 2H), 7.24 (m, 2H), 6.52 1110, 820 (d, J = 15.6 Hz, 1H), 6.38 (dd, J = 15.6, 7.6 Hz, 1H), 6.02 (br s, 1H), 4.53 (d, J = 6.0 Hz, 2H), 4.14 (m, 1H), 1.38 (m, 1H)), 1.00 (m, 2H), 0.77 (m, 2H) CC18 119- 501.88 7.48 (m, 2H), 7.41 (s, 3435, 1644, 123 ([M − H]⁻) 1H), 7.36 (d, J = 8.0 Hz, 1111, 817 1H), 7.23 (m, 2H), 6.52 (d, J = 16.0 Hz, 1H), 6.39 (dd, J = 16.0, 8.0 Hz, 1H), 6.13 (br s, 1H), 4.56 (d, J = 6.0 Hz, 2H), 4.15 (m, 1H), 3.13 (m, 2H) CC19 530 7.41 (m, 2H), 7.24 (m, 3435, 1644, ([M + H]⁺) 1H), 6.53 (d, J = 16.0 1111, 817 Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 4.53 (m, 2H), 4.10 (m, 1H), 3.42 (m, 2H), 2.97 (s, 3H), 2.78 (m, 2H) CC20 512 7.42 (m, 3H), 7.24 (m, 3293, 1633, ([M + H]⁺) 1H), 6.54 (d, J = 15.6 1110, 820 Hz, 1H), 6.34 (dd, J = 15.6, 8.0 Hz, 1H), 6.03 (m 1H), 4.53 (d, J = 6.0 Hz, 1H), 4.10 (m, 1H), 1.19 (m, 1H), 1.00 (m, 2H), 0.77 (m, 2H) CC21 55-58 493.99 (DMSO-d₆) 8.62 (m, ([M − H]⁻) 1H), 7.95 (s, 1H), 7.85 (m, 1H), 7.66 (m, 3H), 7.47 (d, J = 8.0 Hz, 1H), 6.98 (dd, J = 16.0, 8.0 Hz, 1H), 6.84 (d, J = 16.0 Hz, 1H), 4.83 (m, 1H), 4.44 (s, 2H), 1.68 (m, 1H), 0.71 (m, 4H) CC22 67-69 530.01 8.62 (m, 1H), 7.90 (s, ([M + H]⁺) 3H), 7.82 (m, 1H), 7.45 (m, 1H), 6.98 (m, 1H), 6.84 (d, J = 16.0 Hz, 1H), 4.82 (m, 1H), 4.4 (s, 2H), 1.66 (m, 1H), 0.72 (m, 4H) CC23 69-71 564.99 9.02 (br s, 1H), 8.54 (br ([M − H]⁻) s, 1H), 8.26 (br s, 1H), 7.48-7.54 (m, 3H), 7.22-7.42 (m, 3H), 6.59-6.62 (m, 2H), 6.38-6.42 (m, 1H), 4.82 (m, 2H), 4.19 (s, 1H) CC24 125- 570.26 7.64 (s, 1H), 7.54 (s, 127 ([M − H]⁻) 2H), 7.46 (s, 2H), 6.62 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 8.4 Hz, 1H), 6.03 (m, 1H), 4.65 (d, J = 6.4 Hz, 2H), 4.14 (m, 1H, ), 3.13 (q, J = 10.6 Hz, 2H) CC25 579.86 7.60 (s, 1H), 7.40 (s, 3297, 1663, ([M − H]⁻) 2H), 7.37 (d, J = 8.0 Hz, 1114, 809 1H), 7.31 (d, J = 8.0 Hz, 1H), 6.53 (d, 1H, J = 16.0 Hz), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 6.17 (br s, 1H), 4.56 (d, J = 6.4 Hz, 2H), 4.12 (m, 1H), 3.15 (q, J = 10.6 Hz, 2H) CC26 129- 539.89 7.59 (s, 1H), 7.39 (m, 131 ([M + H]⁺) 2H), 7.30 (s, 1H), 6.53 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 6.06 (br s, 1H), 4.42 (d, J = 4.4 Hz, 2H), 4.12 (m, 1H), 1.35 (br s, 1H), 0.95 (br s, 2H), 0.75 (m, 2H) CC27 519.95 7.39 (s, 2H), 7.33 (t, J = 3306, 1786 ([M − H]⁻) 7.6 Hz, 1H), 7.14 (m, 2H), 6.56 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 7.6 Hz, 1H), 6.06 (br s, 1H), 4.52 (d, J = 16.0 Hz, 2H), 4.08 (m, 1H), 3.90 (s, 2H), 3.13 (m, 2H) CC28 477.93 7.39 (s, 2H), 7.35 (m, 3625, 1747 ([M − H]⁻) 1H), 7.14 (m, 2H), 6.55 (d, J = 15.6 Hz, 1H), 6.33 (dd, J = 15.6, 8.0 Hz, 1H), 5.93 (br s, 1H), 4.49 (d, J = 16.0 Hz, 2H), 4.10 (m, 1H), 1.36 (m, 1H), 1.00 (m, 2H), 0.77 (m, 2H) CC29 620.86 8.58 (d, J = 4.6 Hz, 1H), 1645, 1115, ([M − H]⁻) 7.74 (m, 1H), 7.62 (m, 2H), 808 7.52 (m, 1H), 7.4 (s, 2H), 7.3 (m, 1H), 7.2 (m, 2H), 6.60 (d, J = 16.0 Hz, 1H), 6.38 (dd, J = 16.0, 8.0 Hz, 1H), 5.02 (s, 1H), 4.8 (s, 1H), 4.8 (d, J = 10 Hz, 2H), 4.10 (m, 1H), 1.8 (m, 1H), 1.2 (m, 2H), 0.6 (m, 2H) CC30 101- 559.75 7.41 (m, 4H), 7.24 (m, 104 ([M − H]⁻) 1H), 6.53 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 6.12 (br s, 1H), 4.53 (m, 2H), 4.10 (m, 1H), 3.42 (m, 2H), 2.91 (s, 3H), 2.78 (m, 2H) CC31 177- 463 7.58 (m, 2H), 7.41 (m, 178 ([M − H]⁻) 3H), 7.24 (m, 1H), 6.53 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 4.70 (br s, 1H), 4.43 (s, 2H), 4.08 (m, 1H), 3.21 (m, 2H), 1.25 (m, 3H); CC32 141- 532.99 7.66 (m, 2H), 7.54 (m, 142 ([M + H]⁺) 1H), 7.41 (s, 2H), 6.62 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 4.59 (s, 3H), 4.19 (m, 1H), 3.25 (m, 2H), 1.15 (m, 2H) CC33 540.88 7.57 (s, 1H), 7.40 (m, 2H), 3338, 1631, ([M − H]⁻) 7.30 (s, 1H), 7.20 1578, 1114, (br s, 1H), 6.53 (d, J = 809 16.0 Hz, 1H), 6.33 (dd, J = 16.0, 8.0 Hz, 1H), 6.06 (br s, 1H), 4.75 (br s, 1H), 4.42 (s, 2H), 4.20 (br s, 1H), 4.15 (m, 2H), 3.20 (m, 2H), 1.15 (m, 3H) CC34 118- 541.40 7.42 (m, 3H), 7.28 (m, 120 ([M + H]⁺) 2H), 6.54 (d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0, 8.0 Hz, 1H), 4.96 (m, 1H), 4.51 (d, J = 5.6 Hz, 2H), 4.12 (m, 1H), 3.69 (t, J = 4.8 Hz, 4H), 3.35 (t, J = 4.8 Hz, 1H) CC35 78-79 547.82 9.95 (br s, 1H), 8.17 (d, ([M + H]⁺) J = 4.8 Hz, 1H), 7.61 (d, J = 6.4 Hz), 7.43 (m, 3H), 7.24 (m, 2H), 6.90 (t, J = 5.6 Hz, 1H), 6.66 (d, J = 8.4 Hz, 1H), 6.54 (d, J = 16.0 Hz, 1H), 6.33 (dd, J = 16.0, 8.0 Hz, 1H), 4.65 (d, J = 6.0 Hz, 1H), 4.09 (m, 1H) CC36 497 7.39 (m, 4H), 7.28 (m, 3350, 1705, ([M − H]⁻) 1H), 6.54 (d, J = 16.0 1114, 808 Hz, 1H), 6.34 (dd, J = 16.0, 8.0 Hz, 1H), 4.97 (br s, 1H), 4.38 (d, J = 6.0 Hz, 2H), 4.10 (m, 1H), 2.9 (s, 3H), 2.7 (s, 3H) CC37 88-91 515.01 7.49 (d, J = 8 Hz, 1H), ([M + H]⁺) 7.41 (d, J = 7.2 Hz, 2H), 7.26 (m, 2H), 6.50 (d, J = 16 Hz, 1H), 6.35 (dd, J = 16.0, 8.0 Hz, 1H), 6.0 (brs, 1H), 5.73 (br s, 1H), 4.80 (br s, 2H), 4.09 (m, 1H), 1.23 (m, 3H) CC38 63-66 526.97 7.48 (d, J = 8 Hz, 1H), ([M + H]⁺) 7.39 (m, 3H), 7.27 (m, 1H), 6.54 (d, J = 16 Hz, 1H), 6.33 (dd, J = 6.0, 8.0 Hz, 1H), 6.17 (br s, 1H), 5.92 (br s, 1H), 5.83 (m, 2H), 5.29 (t, J = 15.4 Hz, 2H), 4.80 (br s, 2H), 4.12 (m, 1H), 4.02 (br s, 2H) CC39 526.09 7.39 (m, 4H), 7.28 (m, 3350, 1705, ([M − H]⁻) 1H), 6.54 (d, J = 16.0 1114, 808 Hz, 1H), 6.34 (dd, J = 16.0, 8.0 Hz, 1H), 4.97 (br s, 1H), 4.38 (d, J = 6.0 Hz, 2H), 4.10 (m, 1H), 1.53 (s, 9H) CC40 159- 580.25 7.46 (m, 5H), 7.29 (m, 160 ([M − H]⁻) 1H), 7.20 (m, 3H), 6.55 (d, J = 16.0 Hz, 1H), 6.37 (dd, J = 16.0, 8.0 Hz, 1H), 5.62 (br s, 1H), 4.55 (d, J = 6.4 Hz, 2H), 4.11 (m, 1H) CC41 512.22 7.48 (m, 1H), 7.43 (m, 1740, 1701, ([M − H]⁻) 3H), 7.38 (m, 1H), 7.23 1114, 808 (s, 1H), 6.55 (d, J = 16.0 Hz, 1H), 6.36 (d, J = 16.0 Hz, 1H), 4.60 (d, 2H), 4.18 (m, 1H), 3.85 (s, 3H) CC42 161- 578.96 (DMSO-d₆) 9.45 (br s, 163 ([M − H]⁻) 2H), 7.90 (s, 2H), 7.75 (s, 1H), 7.46 (br s, 1H), 7.28 (br s, 1H), 6.93 (m, 1H), 6.75 (br s, 1H), 4.80 (m, 1H), 4.40 (br s, 2H), 3.90 (br s, 2H) CC43 140- 505.39 8.11 (d, J = 4.0 Hz, 1H), 142 ([M + H]⁺) 7.40 (m, 5H), 7.22 (m, 1H), 6.61 (m, 2H), 6.35 (m, 2H), 4.94 (br s, 1H) 4.61 (d, J = 6.4 Hz, 2H), 4.11 (m, 1H) CC44 536.88 8.41 (s, 1H), 7.77 (s, 3320, 1674, ([M − H]⁻) 1H), 7.47 (br s, 1H), 1114, 808 7.40 (s, 2H), 6.58 (d, J = 16.0 Hz, 1H), 6.45 (dd, J = 16.0, 8.0 Hz, 1H), 4.68 (d, J = 4.0 Hz, 2H), 4.14 (m, 1H), 3.24 (q, J = 10.8 Hz, 2H) CC45 494.88 8.41 (s, 1H), 7.76 (s, 3309, 1659, ([M − H]⁻) 1H), 7.40 (s, 2H), 7.15 1115, 808 (br s, 1H), 6.58 (d, J = 16.0 Hz, 1H), 6.44 (dd, J = 16.0, 8.0 Hz, 1H), 4.67 (d, J = 4.4 Hz, 2H), 4.16 (m, 1H), 1.57 (m, 1H), 1.04 (m, 2H), 0.87 (m, 2H) CC46 151- 554.04 8.06 (m, 1H), 7.61 (m, 153 ([M − H]⁻) 4H), 7.48 (s, 2H), 7.44 (d, J = 8.0 Hz, 1H), 7.38 (m, 1H), 6.42 (m, 1H), 5.92 (br s, 1H), 4.92 (m, 2H), 4.24 (m, 1H), 3.12 (m, 2H) CC47 478.09 8.06 (m, 2H), 7.61 (m, 3309, 1659, ([M + H]⁺) 4H), 7.48 (s, 2H), 7.44 1115, 808 (d, J = 8.0 Hz, 1H), 7.38 (m, 2H), 6.42 (m, 1H), 4.92 (s, 2H), 1.36 (m, 1H), 1.00 (m, 2H), 0.77 (m, 2H) CC48 511.05 8.06 (m, 2H), 7.61 (m, 3309, 1659, ([M + H]⁺) 3H), 7.48 (s, 2H), 7.44 1115, 808 (d, J = 8.0 Hz, 1H), 7.38 (m, 2H), 6.42 (m, 1H), 4.92 (s, 2H), 1.36 (m, 1H), 1.00 (m, 2H), 0.77 (m, 2H) CC49 84-87 515.33 8.06 (m, 1H), 7.98 (m, ([M + H]⁺). 1H), 7.61 (m, 3H), 7.48 (s, 2H), 7.44 (d, J = 8.0 Hz, 1H), 7.38 (m, 2H), 6.42 (m, 1H), 4.92 (s, 2H), 4.6 (br s, 1H), 4.24 (m, 1H), 3.21 (m, 2H), 1.2 (t, J = 4.6 Hz, 3H) CC50 138- 461.32 9.81 (s, 1H), 7.90 (s, 140 ([M − 1H]⁻)) 1H), 7.84 (s, 2H), 7.34 (d, J = 8.4 Hz, 2H), 6.65 (d, J = 15.6 Hz, 1H), 6.61 (m, 1H), 6.57 (s, 1H), 6.48 (dd, J = 15.6, 8.8 Hz, 1H), 4.74 (m, 1H), 1.64 (m, 1H), 0.75 (m, 4H); CC51 149- 505.31 7.56 (br s, 1H), 7.4 (s, 150 ([M − H]⁻) 3H), 7.3 (m, 3H), 7.05 (br s, 1H), 6.8 (d, J = 6 Hz, 2H), 6.57 (m, 2H), 6.20 (m, 2H), 4.05 (m, 1H), 3.2 (q, J = 10.4 Hz, 2H) CC52 464.87 7.40 (s, 2H), 7.18 (s, 3309, 1659, ([M − H]⁻) 1H), 7.08 (s, 1H), 6.85 1115, 808 (m, 1H), 6.45 (m, 1H), 6.20 (m, 1H), 5.55 (s, 1H), 4.08 (m, 1H), 1.30-1.10 (m, 4H), 1.90 (m, 1H) CC53 506 7.40 (s, 2H), 7.18 (s, 3309, 1659, ([M + H]⁺) 1H), 7.08 (s, 1H), 6.85 1115, 808 (m, 1H), 6.45 (m, 1H), 6.20 (m, 1H), 5.55 (s, 1H), 4.08 (m, 1H), 3.21 (m, 2H) CC54 504 7.28 (s, 2H), 7.25 (m, ([M + H]⁺) 2H), 7.10 (d, J = 8.0 Hz, 2H), 6.89 (d, J = 11.4 Hz, 1H), 6.07 (br s, 1H), 6.01 (m, 1H), 4.51 (d, J = 5.8 Hz, 2H), 4.34 (m, 1H), 3.12 (q, J = 7.5 Hz, 2H) DC1 93-97 398.05 8.56 (s, 1H), 8.11 (s, ([M + H]⁺) 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 8.4 Hz, 2H), 7.38 (t, J = 1.8 Hz, 1H), 7.29 (s, 2H), 6.62 (d, J = 15.6 Hz, 1H), 6.42 (dd, J = 15.6, 8.2 Hz, 1H), 4.15 (m, 1H) DC2 363.0746 8.59 (s, 1H), 8.13 (s, 3121, 1524, (363.075) 1H), 7.69 (d, J = 8.5 Hz, 1251, 1165, 2H), 7.55 (d, J = 8.5 Hz, 1119 2H), 7.41-7.29 (m, 4H), 6.64 (d, J = 15.7 Hz, 1H), 6.47 (dd, J = 15.9, 8.0 Hz, 1H), 4.17 (m, 1H) DC3 329.1144 8.56 (s, 1H), 8.11 (s, 1521, 1246, (329.114) 1H), 7.65 (d, J = 8.4 Hz, 1219, 1162, 2H), 7.52 (d, J = 8.3 Hz, 1152, 1107 2H), 7.40 (m, 5H), 6.61 (d, J = 15.8 Hz, 1H), 6.51 (dd, J = 15.9, 7.7 Hz, 1H), 4.18 (m, 1H) DC4 364.11 8.56 (s, 1H), 8.10 (s, 1H), 3147, 1528, ([M + H]⁺) 7.66 (d, J = 2.0 Hz, 2H), 1494, 1246, 7.52 (d, J = 8.8 Hz, 2H), 1165, 1108 7.38 (d, J = 2.4 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 6.61 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 7.6 Hz, 1H), 4.15 (m, 1H) DC5 344.25 8.54 (s, 1H), 8.10 (s, 1H), 3122, 3047, ([M + H]⁺) 7.62 (d, J = 8.3 Hz, 2H), 1523, 1252, 7.50 (d, J = 8.4 Hz, 2H), 1160, 1107 7.25 (d, J = 8.3 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 6.60 (d, J = 16.0 Hz, 1H), 6.51 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H), 2.37 (s, 3H) DC6 360.28 8.55 (s, 1H), 8.10 (s, 1H), 3124, 2936, ([M + H]⁺) 7.65 (d, J = 8.8 Hz, 2H), 1522, 1249, 7.52 (d, J = 8.8 Hz, 2H), 1160 7.32 (d, J = 8.8 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 6.60 (d, J = 16.0 Hz, 1H), 6.56 (dd, J = 16.0, 7.4 Hz, 1H), 4.15 (m, 1H), 3.82 (s, 3H) DC7 348 8.55 (s, 1H), 8.10 (s, 1H), 3141, 1512, ([M + H]⁺) 7.62 (d, J = 8.8 Hz, 2H), 1246, 1118 7.5 (d, J = 8.4 Hz, 2H), 7.38 (m, 2H), 7.12 (m, 2H), 6.61 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 7.6 Hz, 1H), 4.15 (m, 1H) DC8 366.13 8.57 (s, 1H), 8.11 (s, 1H), 3116, 1628, ([M + H]⁺) 7.65 (d, J = 7.2 Hz, 2H), 1524, 1252, 7.52 (d, J = 8.0 Hz, 2H), 1168, 1118 6.95 (m, 2H), 6.82 (m, 1H), 6.65 (d, J = 16.0 Hz, 1H), 6.50 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H) DC9 348.11 8.71 (s, 1H), 8.20 (s, 1H), 3115, 1525, ([M + H]⁺) 7.70 (d, J = 8.0 Hz, 2H), 1248, 1174 7.57 (d, J = 8.0 Hz, 2H), 7.40 (m, 1H), 7.19 (m, 3H), 6.60 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.4 Hz, 1H), 4.15 (m, 1H) DC10 348.11 8.75 (s, 1H), 8.20 (s, 1H), 3114, 1526, ([M + H]⁺) 7.72 (d, J = 8.4 Hz, 2H), 1259, 1238, 7.6 (d, J = 8.4 Hz, 2H), 1193, 1114 7.20-7.40 (m, 4H), 6.60 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H,), 4.60 (m, 1H) DC11 75.5- 358.14 8.55 (s, 1H), 8.10 (s, 78.5 ([M + H]⁺) 1H), 7.65 (d, J = 8.8 Hz, 2H), 7.52 (d, J = 8.4 Hz, 2H), 7.01 (s, 3H), 6.60 (d, J = 16.0 Hz, 1H), 6.51 (dd, J = 16.0, 7.8 Hz, 1H), 4.15 (m, 1H), 2.34 (s, 6H) DC12 398.05 8.58 (s, 1H), 8.10 (s, 3055, 2930, ([M + H]⁺) 1H), 7.68 (d, J = 8.4 Hz, 1523, 1250, 2H), 7.53 (m, 4H), 7.2 1165 (s, 1H) 6.62 (d, J = 15.6 Hz, 1H), 6.44 (dd, J = 15.6, 8.0 Hz, 1H), 4.15 (m, 1H) DC13 396.16 8.58 (s, 1H), 8.10 (s, 3108, 1523, ([M + H]⁺) 1H), 7.62 (d, J = 8.4 Hz, 1249, 1166, 2H), 7.55 (m, 4H), 7.25 1127 (m, 1H), 6.64 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 4.90 (m, 1H) DC14 398.05 8.58 (s, 1H), 8.10 (s, 1H), 3117, 2925, ([M + H]⁺) 7.62 (d, J = 8.4 Hz, 2H), 1526, 1246, 7.55 (m, 4H), 7.25 1172, 1117 (m, 1H), 6.67 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 5.00 (m, 1H) DC15 397.95 8.58 (s, 1H), 8.10 (s, 1H), 3120, 1524, ([M + H]⁺) 7.66 (d, J = 8.0 Hz, 2H), 1267, 1176, 7.52 (m, 3H), 7.40 1112 (d, J = 8.0 Hz, 1H), 7.30 (dd, J = 8.4, 2.9 Hz, 1H), 6.64 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 4.90 (m, 1H) DC16 466 8.61 (s, 1H), 8.13 (s, ([M + H]⁺) 1H), 7.92 (s, 1H), 7.86 (s, 2H), 7.70 (d, J = 7.0 Hz, 2H), 7.54 (d, J = 7.0 Hz, 2H), 6.67 (d, J = 16.0 Hz, 1H), 6.46 (dd, J = 16.0, 8.0 Hz, 1H), 4.35 (m, 1H) DC17 430.06 8.58 (s, 1H), 8.1 (s, 1H), 3122, 3076, ([M + H]⁺) 7.68 (d, J = 8.4 Hz, 2H), 2929, 1523, 7.54 (d, J = 8.4 Hz, 2H), 1250, 1168, 7.51 (s, 1H), 7.42 (s, 1H), 1114 6.68 (d, J = 16.0 Hz, 1H), 6.35 (dd, J = 16.0, 8.0, Hz, 1H), 4.98 (m, 1H) DC18 92-95 429.91 8.57 (s, 1H), 8.11 (s, 1H), ([M + H]⁺) 7.69 (d, J = 8.8 Hz, 2H), 7.54 (d, J = 8.4 Hz, 2H), 7.42 (s, 2H), 6.65 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 4.10 (m, 1H) DC19 97-99 430.321 8.58 (s, 1H), 8.12 (s, 1H), ([M + H]⁺) 7.68 (d, J = 8.0 Hz, 2H), 7.64 (s, 1H), 7.59 (s, 1H), 7.55 (m, 3H), 6.60 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 4.22 (m, 1H) DC20 427.0463 8.58 (s, 1H), 8.15 (s, 1H), 2937, 1524, (427.0466) 7.70 (d, J = 8.4 Hz, 2H), 1482, 1278, 7.58 (d, J = 8.4 Hz, 2H), 1249, 1166, 7.36 (s, 2H), 6.62 1112 (d, J = 16.0 Hz, 1H), 6.43 (dd, J = 16.0, 8.0 Hz, 1H), 4.12 (m, 1H), 3.88 (s, 3H) DC21 412.04 8.42 (s, 1H), 7.60 (d, J = 3108, 1572, ([M + H]⁺) 8.0 Hz, 2H), 7.50 (d, J = 1531, 1242, 8.0 Hz, 2H), 7.40 (s, 1172, 1104 1H), 7.22 (s, 2H), 6.60 (d, J = 16.0 Hz, 1H), 6.42 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H), 2.5 (s, 3H) DC22 147- 441.01 8.62 (s, 1H), 7.78 (d, J = 149 ([M − H]⁻) 8.0 Hz, 2H), 7.60 (d, J = 8.0 Hz, 2H), 7.40 (s, 1H), 7.30 (s, 2H), 6.67 (d, J = 16.0 Hz, 1H), 6.48 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H) DC23 412.05 7.95 (s, 1H), 7.35 (d, J = 1112, 799 ([M + H]⁺) 8.0 Hz, 2H), 7.46 (d, J = 8.0 Hz, 2H), 7.39 (s, 1H), 7.29 (s, 2H), 6.67 (d, J = 16.0 Hz, 1H), 6.45 (dd, J = 16.0, 8.0 Hz, 1H), 4.12 (m, 1H), 2.51 (s, 3H) DC24 133- 440.03 8.10 (s, 1H), 7.52 (d, J = 134 ([M + H]⁺) 8.0 Hz, 2H), 7.42-7.38 (m, 3H), 7.28 (s, 2H), 6.67 (d, J = 16.0 Hz, 1H), 6.45 (dd, J = 16.0, 8.0 Hz, 1H), 4.16 (m, 1H), 2.79 (s, 3H) DC25 442.02 7.97 (s, 1H), 7.59 (d, J = 1167, 1114, ([M − H]⁻) 8.0 Hz, 2H), 7.53 (d, J = 800 8.0 Hz, 2H), 7.38 (m, 1H), 7.29 (s, 2H), 6.65 (d, J = 16.0 Hz, 1H), 6.42 (dd, J = 16.0, 8.0 Hz, 1H), 4.17 (m, 1H), 2.74 (s, 3H) DC26 464.03 8.12 (s, 1H), 7.49 (d, J = 1689, 1253, ([M − H]⁻) 8.0 Hz, 2H), 7.40-7.37 1166, 1114, (m 3H), 7.28 (s, 2H), 979, 964 6.66 (d, J = 16.0 Hz, 1H), 6.44 (dd, J = 16.0, 8.0 Hz, 1H), 4.14 (m, 1H), 3.22 (m, 1H), 1.09-1.16 (m, 4H) DC27 473.94 8.19 (s, 1H), 7.64 (d, J = 1571, 1331, ([M − H]⁻) 7.2 Hz, 2H), 7.55 (d, 7.2 1170, 1113, Hz, 2H), 7.39 (s, 1H), 764 7.30 (s, 2H), 6.62 (d, J = 16.0 Hz, 1H), 6.42 (dd, J = 8.0, 16.0 Hz, 1H), 4.18 (m, 1H), 3.58 (s, 3H) DC28 421.22 8.79 (s, 1H), 8.18 (s, 3126, 2233, ([M + H]⁺) 1H), 7.80 (m, 3H), 7.52 1516, 1250, (m, 2H), 7.24 (m, 1H), 1165, 1109 6.63 (d, J = 16.0 Hz, 1H), 6.54 (d, J = 16.0, 7.6 Hz, 1H), 4.19 (m, 1H) DC29 421.22 8.80 (s, 1H), 8.2 (s, 1H), 3005, 1716, ([M + H]⁺) 7.75-7.82 (m, 3H), 1363, 1223 7.41 (t, J = 2 Hz, 1H), 7.26 (m, 2H), 6.65 (d, J = 16.0 Hz, 1H), 6.52 (dd, J = 16.0, 7.6 Hz, 1H), 4.16 (m, 1H) DC30 489.17 8.81 (s, 1H), 8.20 (s, 2964, 2234, ([M + H]⁺) 1H), 7.94 (s, 1H), 7.85 1289, 1166, (m, 3H), 7.79 (m, 2H), 1136 6.70 (d, J = 16.0 Hz, 1H), 6.58 (dd, J = 16.0, 8.0 Hz, 1H), 4.35 (m, 1H) DC31 117- 455.27 8.80 (s, 1H), 8.20 (s, 118 ([M + H]⁺) 1H), 7.82 (m, 3H), 7.4 (s, 2H), 6.62 (d, J = 16.0 Hz, 1H), 6.52 (dd, J = 16.0, 8.0 Hz, 1H), 4.18 (m, 1H) DC32 388.0705 8.82 (s, 1H), 8.22 (s, 3126, 2234, (388.0703) 1H), 7.82-7.78 (m, 3H), 1520, 1280, 7.38-7.30 (m, 3H), 6.62 1164, 1112 (d, J = 16.1 Hz, 1H), 6.56 (dd, J = 16.1, 6.8 Hz, 1H), 4.18 (m, 1H) DC33 455.22 8.80 (s, 1H), 8.20 (s, 3122, 3086, ([M − H]⁻) 1H), 7.82-7.80 (m, 3H), 2234, 1517, 7.70-7.50 (m, 3H), 6.65 1327, 1168, (d, J = 16.9 Hz, 1H), 1113 6.54 (dd, J = 16.9, 6.8 Hz, 1H), 4.25 (m, 1H) DC34 452.0412 8.85 (s, 1H), 8.23 (br s, 3122, 2934, (452.0419) 1H), 7.83-7.78 (m, 3H), 2231, 1516, 7.33 (s, 2H), 6.69 (d, J = 1480, 1248, 14.9 Hz, 1H), 6.50 (dd, 1211, 1165, J = 14.9, 7.2 Hz, 1H), 1111 4.15 (m, 1H), 3.90 (s, 3H) DC35 439.01 8.60 (s, 1H), 8.20 (s, 2233, 1518, ([M − H]⁻) 1H), 7.82 (m, 3H), 7.28 1250, 1169, (m, 2H), 6.65 (d, J = 1035, 817 16.0 Hz, 1H), 6.48 (dd, J = 16.0, 8.0 Hz, 1H), 4.20 (m, 1H) DC36 437.25 8.70 (s, 1H), 7.80 (m, 2927, 2233, ([M + H]⁺) 3H), 7.40 (s, 1H), 7.28 1572, 1531, (s, 2H), 6.63 (d, J = 16.0 1248, 1166, Hz, 1H), 6.50 (dd, J = 1112 16.0, 8.0 Hz, 1H), 4.18 (m, 1H), 2.50 (s, 1H) DC37 109- 466.10 8.86 (s, 1H), 7.89 (m, 111 ([M − H]⁻) 3H), 7.40 (s, 1H), 7.30 (s, 2H), 6.68 (d, J = 16.0 Hz, 1H), 6.57 (dd, J = 16.0, 8.0 Hz, 1H), 4.18 (m, 1H) DC38 96-98 436.11 8.58 (s, 1H), 7.75 (m, ([M − H]⁻) 3H), 7.40 (s, 1H), 7.28 (s, 2H), 6.61 (d, J = 16.0 Hz, 1H), 6.42 (dd, J = 16.0, 8.2 Hz, 1H), 4.40 (br s, 2H), 4.15 (m, 1H) DC39 224- 480.30 8.65 (s, 1H), 8.18 (br s, 3352, 2237, 226 ([M + H]⁺) 1H), 7.80-7.70 (m, 3H), 1707, 1163, 7.40 (s, 1H), 7.27 (s, 841 2H), 7.36 (m, 1H), 7.28 (m, 2H), 6.60 (d, J = 16.8 Hz, 1H), 6.47 (m, 1H), 4.16 (m, 1H), 2.40 (br s, 3H) DC40 70-73 436.11 8.86 (s, 1H), 7.88 (m, ([M − 2H]⁻) 3H), 7.44 (s, 2H), 6.67 (d, J = 16.0 Hz, 1H), 6.56 (dd, J = 16.0 7.6 Hz, 1H), 4.19 (m, 1H) DC41 72-75 469.95 (DMSO-d₆) 8.72 (s, ([M − H]⁻) 1H), 8.26 (s, 1H), 8.01 (d, J = 8.4 Hz, 1H), 7.91 (s, 2H), 7.77 (d, J = 8.4 Hz, 1H), 6.42 (dd, J = 15.6, 9.2 Hz, 1H), 6.83 (d, J = 15.6 Hz, 1H), 5.87 (s, 2H), 4.89 (m, 1H) DC42 104- 609.98 8.78 (s, 2H), 7.83 (s, 2234, 1714, 107 ([M + H]⁺) 1H), 7.80 (m, 2H), 7.42 1114, 807 (s, 2H), 6.65 (d, J = 16.4 Hz, 1H), 6.51 (dd, J = 16.4, 7.8 Hz, 1H), 4.17 (m, 1H), 4 2.16 (m, 2H), 1.25 (m, 4H), 1.00 (m, 4H), DC43 109- 540.04 (DMSO-d₆) 10.94 (br s, 3233, 2233, 112 ([M + H]⁺) 1H), 8.36 (s, 1H), 8.08 1699, 1114, (m, J = 8.4 Hz, 1H), 807 7.91 (s, 2H), 7.84 (d, J = 8.4 Hz, 1H), 7.13 (dd, J = 15.6, 9.2 Hz, 1H), 6.87 (d, J = 15.6 Hz, 1H), 4.92 (m, 1H), 1.99 (br s, 1H), 0.82 (s, 4H) DC44 435.26 8.33 (s, 1H), 8.23 (s, 2236, 1510, [M − H]⁻ 1H), 7.66 (s, 1H), 7.60 1114, 801 (s, 1H), 7.41 (m, 1H), 7.28 (m, 2H), 6.62 (d, J = 16.0 Hz, 1H), 6.51 (dd, J = 16.0, 7.8 Hz, 1H), 4.16 (m, 1H), 2.20 (s, 3H) DC45 75-78 468.87 8.36 (s, 1H), 8.23 (s, [M − H]⁻ 1H), 7.66 (s, 1H), 7.60 (s, 1H), 7.41 (s, 2H), 6.62 (d, J = 16.4 Hz, 1H), 6.51 (dd, J = 16.4, 7.6 Hz, 1H), 4.16 (m, 1H), 2.20 (s, 3H) DC46 411.4 8.83 (s, 1H), 8.21 (s, 1H), ¹³C NMR (δ)³ ([M]⁺) 7.83 (d, J = 8.5 Hz, 1H), 155.63, 153.27, 7.61 (d, J = 1.9 Hz, 1H), 153.12, 143.01, 7.52 (dd, J = 8.4, 137.89, 136.25, 1.9 Hz, 1H), 7.28 (d, J = 134.03, 133.88, 3.8 Hz, 2H), 6.93 (d, J = 132.23, 131.23, 11.5 Hz, 1H), 6.26-6.20 (m, 131.18, 129.20, 1H), 4.22 (m, 1H) 126.17, 125.04, 124.99 DC47 139- 474.16 8.51 (s, 1H), 8.14 (s, 141 ([M − H]⁻) 1H), 7.75 (s, 1H), 7.5 (m, 2H), 7.4 (s, 1H), 7.30 (m, 2H), 6.60 (d, J = 16.0 Hz, 1H), 6.50 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H) DC48 124- 414.05 8.69 (s, 1H), 8.14 (s, 126 [M − H]⁻ 1H), 7.96 (d, J = 4.8 Hz, 1H), 7.39-7.27 (m, 5H), 6.95 (d, J = 16.0 Hz, 1H), 6.51 (dd, J = 16.0, 7.6 Hz, 1H), 4.13 (m, 1H) DC49 81-83 463.96 8.57 (s, 1H), 8.14 (s, [M − H]⁻ 1H), 7.60 (m, 2H), 7.44 (m, 3H), 6.95 (d, J = 16.0 Hz, 1H), 6.51 (dd, J = 16.0, 7.6 Hz, 1H), 4.13 (m, 1H) DC50 140- 430.07 8.56 (s, 1H), 8.13 (s, 1110, 803 143 [M − H]⁻) 1H), 7.59 (d, J = 1.2 Hz, 2H), 7.44 (m, 2H), 7.28 (m, 2H), 6.61 (d, J = 16.0 Hz, 1H), 6.47 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H) DC51 118- 464.22 8.32 (s, 1H), 8.15 (s, 121 ([M − H]⁻) 1H), 7.82 (s, 1H), 7.73 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 8.4 Hz, 1H), 7.41 (s, 1H), 7.29 (s, 2H), 6.70 (d, J = 15.6 Hz, 1H), 6.50 (dd, J = 15.6, 8.0 Hz, 1H), 4.20 (m, 1H) DC52 9.99 (s, 1H), 8.42 (s, 3123, 3079, 1H), 8.12 (s, 1H), 8.01 2925, 1692, (s, 1H), 7.68 (m, 1H), 1571, 1512, 7.44 (m, 1H), 7.33 (m, 1253, 1164, 1H), 7.22 (s, 2H), 6.62 1111 (d, J = 16.7 Hz, 1H), 6.45 (dd, J = 16.7, 9.3 Hz, 1H), 4.10 (m, 1H) DC53 8.30 (m, 1H), 8.00 (br s, 3250, 3043, 1H), 7.75 (m, 1H), 7.68 1683, 1116 (m, 1H), 7.55 (m, 1H), 7.36 (m, 1H), 7.28 (m, 2H), 6.70 (m, 1H), 6.58 (br s, 1H), 6.33 (m, 1H), 5.88 (m, 2H), 4.10 (m, 1H) DC54 56-58 441.07 8.40 (s, 1H), 8.13 (s, ([M − H]⁻) 1H), 8.02 (s, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.4 (s, 1H), 7.29 (m, 2H), 6.69 (d, J = 15.6 Hz, 1H), 6.57 (dd, J = 15.6, 7.8 Hz, 1H), 4.15 (m, 1H) DC55 412.97 8.37 (s, 1H), 8.18 (s, ([M + H]⁺) 1H), 7.39 (s, 1H), 7.30 (m, 2H), 7.19 (d, J = 8.0 Hz, 1H), 6.90 (m, 2H), 6.55 (d, J = 15.6 Hz, 1H), 6.38 (dd, J = 15.6, 8.2 Hz, 1H), 4.20 (m, 1H), 2.50 (br s, 2H) DC56 175- 453 9.59 (br s, 1H), 8.55 (s, 177 ([M − H]⁻) 1H), 8.47 (s, 2H), 8.23 (s, 1H), 7.30 (m, 4H), 6.62 (d, J = 16.0 Hz, 1H), 6.40 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H), 2.20 (s, 3H) DC57 426.0627 8.33 (s, 1H), 8.16 (s, 3342, 3112, (426.0626) 1H), 7.38 (s, 1H), 7.29 2931, 1606, (s, 2H), 7.15 (d, J = 7.6 1583, 1574, Hz, 1H), 6.80 (d, J = 7.6 1528, 1153 Hz, 1H), 6.74 (m, 1H), 6.60 (d, J = 15.6 Hz, 1H), 6.35 (dd, J = 15.6, 8.4 Hz, 1H), 5.40 (br s, 1H), 4.15 (m, 1H), 2.90 (s, 3H) DC58 94-97 440.0424 (DMSO-d₆) 8.76 (s, 3403, 3304, (440.0419) 1H), 8.16 (s, 1H), 7.90 3178, 1674, (br s, 1H), 7.83 (s, 1H), 1571, 1169, 7.70 (d, J = 7.9 Hz, 1H), 1108 7.71-7.67 (m, 3H), 7.58 (d, J = 7.9 Hz, 1H), 7.52 (br s, 1H), 7.00 (dd, J = 15.8, 8.7 Hz, 1H), 6.85 (d, J = 15.8 Hz, 1H), 4.85 (m, 1H) DC59 87-90 (DMSO-d₆) 9.00 (s, 1H), 8.63 (s, 1H), 8.17 (s, 1H), 7.70-7.59 (m, 5H), 7.00 (dd, J = 16.2, 9.7 Hz, 1H), 6.85 (d, J = 16.2 Hz, 1H), 5.90 (br s 2H), 4.83 (m, 1H) DC60 469.0577 8.32 (s, 1H), 8.10 (s, 2987, 1725, (469.0572) 1H), 7.97 (s, 1H), 7.65 1518, 1275, (d, J = 8.1 Hz, 1H), 7.47 1166, 1113 (d, J = 8.1 Hz, 1H), 7.40 (m, 1H), 7.28 (s, 2H), 6.62 (d, J = 16.5 Hz, 1H), 6.49 (dd, J = 16.5, 7.7 Hz, 1H), 4.23-4.04 (m, 3H), 1.15 (t, J = 8.0 Hz, 3H) DC61 130- 442.15 (DMSO-d₆) 9.90 (s, 132 ([M + H]⁺) 1H), 8.17 (s, 1H), 8.15 (m, 1H), 7.90 (m, 1H), 7.71 (m, 2H), 7.67 (m, 1H), 7.62 (d, J = 7.3 Hz, 1H), 7.03 (dd, J = 16.5, 8.3 Hz, 1H), 6.62 (d, J = 16.5 Hz, 1H), 4.87 (m, 1H) DC62 412.10 8.27 (s, 1H), 8.23 (s, 1513, 1252, ([M + H]⁺) 1H), 7.40 (m, 3H), 7.30 1166, 1112, (m, 3H), 6.64 (d, J = 801 16.0 Hz, 1H), 6.45 (dd, J = 16.0, 8.0 Hz, 1H), 4.19 (m, 1H), 2.21 (s, 3H) DC63 446.01 8.26 (s, 1H), 8.12 (s, 2928, 2525, ([M + H]⁺) 1H), 7.42 (s, 2H), 7.18- 1249, 1169, 7.28 (m, 3H), 6.62 (d, 1114, 809 J = 15.6 Hz, 1H), 6.39 (dd, J = 15.6, 9.4 Hz, 1H), 4.10 (m, 1H), 2.25 (s, 3H) DC64 475.03 8.84 (d, J = 5.8 Hz, 2H), 1683, 1167, ([M + H]⁺) 8.33 (s, 1H), 8.20 (s, 650, 479 1H), 7.75 (m, 1H), 7.60 (d, J = 28.6 Hz, 1H), 7.58-7.48 (m, 3H), 7.42 (m, 1H), 7.28 (s, 2H), 6.71 (d, J = 16.9 Hz, 1H), 6.39 (dd, J = 16.9, 8.2 Hz, 1H), 4.15 (m, 1H) DC65 412.05 8.55 (s, 1H), 8.12 (s, 722, 111 ([M + H]⁺) 1H), 7.55 (m, 3H), 7.39 (m, 1H), 7.30 (d, J = 1.6 Hz, 1H), 6.85 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 8.0 Hz, 1H), 4.17 (m, 1H), 2.40 (s, 3H) DC66 60-61 468.26 8.59 (s, 1H), 8.14 (s, ([M + H]⁺) 1H), 7.94 (s, 1H), 7.70 (d, J = 8.0 Hz, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.43 (s, 2H), 7.23 (d, J = 16.0 Hz, 1H), 6.41 (dd, J = 16.0, 8.0 Hz, 1H), 4.20 (m, 1H) DC67 133- 432.30 8.59 (s, 1H), 8.12 (s, 800, 114 134 ([M + H]⁺) 1H), 7.78 (br s, 1H), 7.71 (m, 1H), 7.62 (m, 1H), 7.39 (s, 1H), 7.32 (s, 2H), 7.03 (d, J = 16.0 Hz, 1H), 6.43 (dd, J = 16.0, 8.0 Hz, 1H), 0.21 (m, 1H) DC68 412.03 8.71 (s, 1H), 8.18 (s, ([M + H]⁺) 1H), 7.71 (d, J = 8.0 Hz, 2H), 7.55 (d, J = 8.0 Hz, 2H), 7.37 (s, 1H), 7.28 (m, 2H), 6.08 (d, J = 16.0 Hz, 1H), 4.26 (m, 1H), 2.05 (s, 3H) DC69 162- 414.03 8.56 (s, 1H), 8.11 (s, 1H), 168 ([M + H]⁺) 7.70 (d, J = 8.5 Hz, 2H), 7.56 (d, J = 8.5 Hz, 2H), 7.54 (m, 2H), 7.40 (m, 1H), 6.91 (d, J = 16.5 Hz, 1H), 6.66 (d, J = 16.5 Hz, 1H) DC70 99- 428.05 8.58 (s, 1H), 8.13 (s, 103 ([M + H]⁺) 1H), 7.73 (d, J = 8.7 Hz, 2H), 7.60 (d, J = 8.7 Hz, 2H), 7.46 (m, 2H), 7.42 (m, 1H), 6.85 (d, J = 16.2 Hz, 1H), 6.40 (d, J = 16.2 Hz, 1H), 3.42 (s, 3H) ^(a1)H NMR spectral data were acquired using a 400 MHz instrument in CDCl₃ except where noted. HRMS data are noted observed value (theoretical value).

TABLE 2A Analytical Data for Compounds in Table 1A. Compound mp (° C.); IR (cm⁻¹); Number [α]_(D) ²⁵ ESIMS ¹H NMR (δ)^(a) ¹⁹F NMR (δ) F1 606.91 (300 MHz, DMSO-d₆) 3427, 1667, ([M + H]⁺) δ 8.96 (bs, 1H), 8.14 (t, 1162, 749 J = 6.6 Hz, 1H), 7.90 (s, 2H), 7.77 (s, 1H), 7.68 (d, J = 8.1 Hz 1H), 7.59 (d, J = 7.8 Hz, 1H), 7.02 (dd, J = 15.9, 9.3 Hz, 1H), 6.78 (d, J = 15.6 Hz, 1H), 4.84- 4.80 (m, 1H), 3.96- 3.87 (m, 2H), 1.40- 1.33 (m, 2H), 1.10- 1.04 (m, 2H) F2 587.0 (300 MHz, DMSO-d₆) 3339, 1668, ([M + H]⁺) δ 8.71 (s, 1H), 8.25 (t, J = 1162, 810 6.3 Hz, 1H), 7.89 (s, 2H), 7.53 (d, J = 8.1 Hz, 1H), 7.45 (s, 1H ), 7.42 (d, J = 8.4 Hz, 1H), 6.89 (dd, J = 15.9, 8.7 Hz, 1H), 6.75 (d, J = 15.5 Hz, 1H), 4.85- 4.77 (m, 1H), 3.94-3.82 (m, 2H ), 2.35 (s, 3H), 1.37 (d, J = 2.7 Hz, 2H), 1.05 (d, J = 2.7 Hz, 2H) F3 650.87 (300 MHz, CDCl₃) δ 3424, 1674, ([M + H]⁺) 7.61 (s, 1H), 7.51 (d, J = 1162, 807 8.1 Hz, 1H), 7.40- 7.39 (m, 2H), 7.14-7.09 (m, 1H), 6.56 (d, J = 15.6 Hz, 1H), 6.43 (dd, J = 15.9, 7.8 Hz, 1H), 4.13-4.08 (m, 1H), 3.99-3.91 (m, 2H), 1.25-1.20 (m, 4H) F4 620.95 (300 MHz, DMSO-d₆) δ 3433, 1642, ([M + H]⁺) 9.01 (s, 1H), 7.99 (t, J = 1162, 750 6.3 Hz, 1H), 7.89 (s, 2H), 7.78-7.75 (m, 1H), 7.61-7.54 (m, 2H), 7.01 (dd, J = 15.9, 9.3 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.85-4.79 (m, 1H), 3.92-3.83 (m, 2H), 2.48-2.41 (m, 2H), 2.23-2.17 (m, 2H), 1.93-1.80 (m, 2H) F5 664.85 (300 MHz, DMSO-d₆) 3292, 1681, ([M + H]⁺) δ 9.03 (s, 1H), 8.00 (t, J = 1163, 745, 6.3 Hz, 1H), 7.94- 558 7.91 (m, 3H), 7.64- 7.56 (m, 2H), 7.02 (dd, J = 9.0 Hz, 1H), 6.78 (d, J = 15.3 Hz, 1H), 4.86-4.79 (m, 1H), 3.94-3.85 (m, 2H), 2.51-2.49 (m, 2H), 2.30-2.20 (m, 2H), 1.88-1.82 (m, 2H) F6 656.98 (300 MHz, DMSO-d₆) 3401, 1672, ([M + H]⁺) δ 9.62 (t, J = 12.0 Hz, 1171, 806 1H), 9.09 (bs, 1H), 8.01 (s, 1H), 7.96-7.87 (m, 4H), 7.11 (dd, J = 15.9, 9.3 Hz, 1H), 6.89 (d, J = 15.9 Hz, 1H), 4.89- 4.83 (m, 1H), 4.62-4.64 (m, 2H), 1.85-1.82 (m, 2H), 1.27-1.23 (m, 2H) F7 158- 553 7.61 (d, J = 8.0 Hz, 160 ([M + H]⁺) 1H), 7.60 (d, J = 1.6 Hz, 1H), 7.39 (m, 3H), 6.57 (s, 1H), 6.53 (d, J = 15.9 Hz, 1H), 6.40 (dd, J = 15.9, 7.8 Hz, 1H), 4.10 (p, J = 9.1, 8.6 Hz, 1H), 1.68 (m, 2H), 1.42 (m, 2H) F8 640.9 (400 MHz, DMSO-d₆) 3461, 1676, ([M + H]⁺) δ 9.02 (s, 1H), 8.11 (t, J = 1165, 808 6.4 Hz, 1H), 8.0 (s, 1H), 7.94-7.88 (m, 4H), 7.10 (dd, J = 15.6, 9.2 Hz, 1H), 6.89 (d, J = 16.4 Hz, 1H), 4.89-4.84 (m, 1H), 3.98-3.89 (m, 2H), 1.39-1.36 (m, 2H), 1.26-1.24 (m, 2H) F8A [α]_(D) ²⁵ = −35.4 641.1 (400 MHz, DMSO-d₆) 3444, 1672, (c, 0.5% ([M + H]⁺) δ 9.02 (s, 1H), 8.10 (t, J = 1165, 808 in 6.4 Hz, 1H), 7.99 (s, CH₂Cl₂) 1H), 7.94-7.87 (m, 4H), 7.09 (dd, J = 15.6 Hz, 9.2 Hz, 1H), 6.88 (d, J = 15.6 Hz, 1H), 4.88-4.84 (m, 1H), 3.95-3.88 (m, 2H), 1.39-1.36 (m, 2H), 1.02-0.99 (m, 2H) F8B [α]_(D) ²⁵ = +36.4 641.0 (400 MHz, DMSO-d₆) 3459, 1672, (c, 0.5% ([M + H]⁺) δ 9.01 (s, 1H), 8.10 (t, J = 1166, 807 in 6.4 Hz, 1H), 7.99 (s, CH₂Cl₂) 1H), 7.94-7.87 (m, 4H), 7.09 (dd, J = 15.6 Hz, 8.8 Hz, 1H), 6.88 (d, J = 15.6 Hz, 1H), 4.88-4.84 (m, 1H), 3.95-3.91 (m, 2H), 1.39-1.36 (m, 2H), 1.02-0.99 (m, 2H) ^(a1)H NMR spectral data were acquired using a 400 MHz instrument in CDCl₃ except where noted. HRMS data are noted observed value (theoretical value).

TABLE 2B Analytical Data for Compounds in Table 1B. Compound IR (cm⁻¹); Number mp (° C.) ESIMS ¹H NMR (δ)^(a) ¹⁹F NMR (δ) P31 561.9 7.61 (d, J = 1.7 Hz, 1H), ¹⁹F NMR ([M − H]⁻) 7.59 (d, J = 8.0 Hz, 1H), (376 MHz, 7.40 (m, 3H), 6.53 (d, J = CDCl₃) 15.9 Hz, 1H), 6.39 (m, δ −68.61, −131.43 2H), 4.10 (p, J = 8.6 Hz, (d, J = 1H), 3.55 (dddd, J = 163.1 Hz), −143.05 15.8, 8.3, 6.1, 3.1 Hz, (d, J = 1H), 1.93 (m, 1H), 1.50 162.9 Hz) (m, 1H) P65 593.1 (300 MHz, DMSO-d₆) δ 3379, 1678, ([M + H]⁺) 9.02 (bs, 1H), 8.13 (t, J = 1161 6.6 Hz, 1H), 7.96- 7.87 (m, 3H), 7.63 (d, J = 8.1 Hz, 1H), 7.51 (dd, J = 15.9, 8.7 Hz, 1H), 7.01-6.94 (m, 2H), 5.00-4.94 (m, 1H), 4.04-3.87 (m, 2H), 1.27-1.24 (m, 2H), 1.01-0.98 (m, 2H) P108 651.0 (400 MHz, DMSO-d₆) δ 3421, 1671, ([M + H]⁺) 8.95 (s, 1H), 8.10 (t, J = 1114, 664, 574 6.4 Hz, 1H), 7.96-7.93 (m, 3H), 7.67-7.60 (m, 2H), 7.03 (dd, J = 15.6, 8.4 Hz, 1H), 6.93 (d, J = 15.6 Hz, 1H), 5.09- 5.05 (m, 1H), 3.96- 3.89 (m, 2H), 1.39- 1.37 (m, 2H), 1.10- 1.07 (m, 2H) P110 641.0 (400 MHz, DMSO-d₆) δ 3293, 1673, ([M + H]⁺) 9.02 (s, 1H), 8.10 (t, J = 1115, 736 6.0 Hz, 1H), 8.00-7.88 (m, 5H), 7.09-7.01 (m, 2H), 5.12 (m, 1H), 3.95- 3.91 (m, 2H), 1.39- 1.37 (m, 2H), 1.01- 1.00 (m, 2H) P153 632.79 (300 MHz, DMSO-d₆) δ 3413, 1668, ([M + H]⁺) 8.94 (bs, 1H), 8.12 (t, J = 1161, 564 6.0 Hz, 1H), 7.90 (s, 1H), 7.67-7.57 (m, 5H), 7.41 (d, J = 7.5 Hz, 1H), 6.99 (dd, J = 15.9, 9.3 Hz, 1H), 6.78 (d, J = 15.6 Hz, 1H), 4.82- 4.79 (m, 1H), 4.01- 3.83 (m, 2H), 1.40- 1.36 (m, 2H), 1.11- 1.07 (m, 2H) P155 622.97 300 MHz, DMSO-d₆) δ 3413, 1668, ([M + H]⁺) 9.01 (bs, 1H), 8.10 (t, J = 1161, 564 6.0 Hz, 1H), 7.97 (s, 1H), 7.92-7.87 (m, 2H), 7.61-7.56 (m, 3H), 7.42 (t, J = 8.1 Hz, 1H), 7.09 (dd, J = 15.6, 8.7 Hz, 1H), 6.90 (d, J = 15.9 Hz, 1H), 4.89- 4.85 (m, 1H), 3.98- 3.90 (m, 2H), 1.39- 1.33 (m, 2H), 1.11- 1.01 (m, 2H) P198 645.0 (300 MHz, DMSO-d₆) δ 3280, 1668, ([M + H]⁺) 8.95 (s, 1H), 8.12 (t, J = 1164, 523 6.0 Hz, 1H), 7.91 (d, J = 0.9 Hz, 1H), 7.67-7.60 (m, 4H), 7.54 (d, J = 9.9 Hz, 1H), 6.99 (dd, J = 15.6, 9.0 Hz, 1H), 6.77 (d, J = 15.3 Hz, 1H), 4.83-4.77 (m, 1H), 3.96-3.91 (m, 2H), 1.40-1.36 (m, 2H), 1.11-1.07 (m, 2H) P200 635.0 (300 MHz, DMSO-d₆) δ 3297, 1675, ([M + H]⁺) 9.02 (s, 1H), 8.13 (d, J = 1166, 565 6.6 Hz, 1H), 7.99-7.87 (m, 3H), 7.69 (s, 1H), 7.63-7.55 (m, 1H), 7.55 (d, J = 9.3 Hz, 1H), 7.09 (dd, J = 15.9, 9.3 Hz, 1H), 6.89 (d, J = 15.6 Hz, 1H), 4.86-4.80 (m, 1H), 3.96-3.87 (m, 2H), 1.41-1.36 (m, 2H), 1.03-0.99 (m, 2H) P243 597.00 (300 MHz, DMSO-d₆) δ 3281, 2929, ([M + H]⁺) 8.94 (s, 1H), 8.10 (t, J = 1679, 1161, 6.0 Hz, 1H), 7.86 (s, 739, 563 1H), 7.66-7.58 (m, 2H), 7.52-7.45 (m, 2H), 7.39-7.36 (m, 1H), 6.91 (dd, J = 15.6, 8.4 Hz, 1H), 6.75 (d, J = 8.4 Hz, 1H), 4.66-4.62 (m, 1H), 4.01-3.85 (m, 2H), 2.35 (s, 3H), 1.37- 1.33 (m, 2H), 1.09- 1.02 (m, 2H) P245 587.2 (300 MHz, DMSO-d₆) δ 3280, 2925, ([M + H]⁺) 9.01 (s, 1H), 8.12 (t, J = 1668, 1163, 6.3 Hz, 1H), 7.91-7.86 750 (m, 3H), 7.53 (s, 1H), 7.49 (d, J = 8.1 Hz, 1H), 7.40 (d, J = 7.2 Hz, 1H), 7.01 (dd, J = 16.2, 8.4 Hz, 1H), 6.81-6.85 (d, J = 15.9 Hz, 1H), 4.72- 4.65 (m, 1H), 3.99- 3.90 (m, 2H), 2.36 (s, 3H), 1.41-1.35 (m, 2H), 1.12-1.11 (m, 2H) P333 594.94 (300 MHz, DMSO-d₆) δ 3252, 1667, ([M + H]⁺) 8.94 (bs, 1H), 8.12(t, J = 1163 6.0 Hz, 1H), 7.85 (s, 1H), 7.66-7.57 (m, 2H), 7.26 (d, J = 6.6 Hz, 2H), 6.89 (dd, J = 15.9, 8.9 Hz, 1H), 6.73 (d, J = 15.9 Hz, 1H), 4.55- 4.52 (m, 1H), 3.96- 3.87 (m, 2H), 2.23 (s, 6H), 1.40-1.36 (m, 2H), 1.10-1.07 (m, 2H) P335 585.4 (300 MHz, DMSO-d₆) δ 3252, 1667, ([M + H]⁺) 9.09 (bs, 1H), 8.12 (t, J = 1163 5.7 Hz, 1H), 7.95 (s, 1H), 7.92-7.85 (m, 2H), 7.27 (d, J = 6.9 Hz, 2H), 6.98 (dd, J = 15.9, 8.7 Hz, 1H), 6.85 (d, J = 15.9 Hz, 1H), 4.89- 4.85 (m, 1H), 3.98- 3.90 (m, 2H), 2.24 (s, 6H), 1.39-1.33 (m, 2H), 1.11-1.01 (m, 2H) P336 571.01 (400 MHz, DMSO-d₆) δ 3283, 1667, ([M + H]⁺) 9.01 (s, 1H), 8.10 (t, J = 1165 6.4 Hz, 1H), 7.93-7.86 (m, 3H), 7.47 (d, J = 7.6 Hz, 1H), 7.40-7.38 (m, 1H), 7.19 (t, J = 9.6 Hz, 1H), 7.00 (dd, J = 16.4, 8.8 Hz, 1H), 6.85 (d, J = 16.0 Hz, 1H), 4.68- 4.64 (m, 1H), 3.97- 3.88 (m, 2H), 2.26 (s, 3H), 1.39-1.36 (m, 2H), 1.02-0.99 (m, 2H) P378 659.00 (300 MHz, DMSO-d₆) δ 3418, 2926, ([M − H]⁻) 8.94 (bs, 1H), 8.10 (bs, 1666, 1163, 1H), 7.92 (s, 1H), 7.80- 749 7.78 (m, 2H), 7.71 (s, 1H), 7.64-7.61 (m, 2H), 7.00 (dd, J = 15.6, 9.0 Hz, 1H), 6.76 (d, J = 15.9 Hz, 1H), 4.81- 4.80 (m, 1H), 3.96- 3.91 (m, 2H), 1.40- 1.37 (m, 2H) 1.10-1.07 (m, 2H) P380 650.93 (400 MHz, DMSO-d₆) δ 3396, 1668, ([M + H]⁺) 9.01 (bs, 1H), 8.10 (t, J = 1164, 772, 8.8 Hz, 1H), 7.99 (s, 566 1H), 7.94-7.87 (m, 2H), 7.81-7.78 (m, 2H), 7.73 (s, 1H), 7.09 (dd, J = 15.6, 8.7 Hz, 1H), 6.88 (d, J = 15.6 Hz, 1H), 4.82-4.80 (m, 1H), 3.95-3.91 (m, 2H), 1.39-1.33 (m, 2H), 1.02-1.00 (m, 2H) P423 704.84 (300 MHz, DMSO-d₆) δ 3418, 2925, ([M + H]⁺) 8.94 (s, 1H), 8.10 (t, J = 1667, 1163 6.6 Hz, 1H), 7.98-7.97 (m, 1H), 7.90 (s, 1H), 7.85 (d, J = 8.2 Hz, 1H), 7.66-7.59 (m, 2H), 7.51-7.48 (m, 1H), 6.96 (dd, J = 15.9, 9.0 Hz, 1H), 6.75 (d, J = 15.9 Hz, 1H), 4.81- 4.75 (m, 1H), 3.96- 3.91 (m, 2H), 1.40- 1.26 (m, 2H), 1.11- 1.07 (m, 2H) P425 694.89 (300 MHz, DMSO-d₆) δ 3373, 2927, ([M + H]⁺) 9.03 (s, 1H), 8.10 (t, J = 1675, 1165, 6.6 Hz, 1H), 7.99-7.97 565 (m, 2H), 7.91-7.89 (m, 2H), 7.86 (d, J = 8.4 Hz, 1H), 7.53-7.50 (m, 1H), 7.07 (dd, J = 15.6, 8.8 Hz, 1H), 6.87 (d, J = 15.9 Hz, 1H), 4.84- 4.78 (m, 1H), 3.99- 3.90 (m, 2H), 1.39- 1.35 (m, 2H), 1.03- 0.99 (m, 2H) P468 628.40 (400 MHz, DMSO-d₆) δ 3417, 1670, ([M + H]⁺) 8.95 (s, 1H), 8.31 (s, 1163, 750, 1H), 8.11 (t, J = 6.4 Hz, 558 1H), 7.92-7.87 (m, 3H), 7.67-7.60 (m, 2H), 6.98 (dd, J = 15.6, 8.7 Hz, 1H), 6.78 (d, J = 15.6 Hz, 1H), 4.99- 4.94 (m, 1H), 3.98- 3.89 (m, 2H), 1.39- 1.33 (m, 2H), 1.09- 1.07 (m, 2H) P470 616.40 (400 MHz, DMSO-d₆) δ 3372, 1669, ([M − H]⁻) 9.01 (bs, 1H), 8.32 (s, 1162, 750 1H), 8.10 (t, J = 8.4 Hz, 1H), 7.93-7.84 (m, 5H), 7.07 (dd, J = 16.4, 8.8 Hz, 1H), 6.90 (d, J = 15.6 Hz, 1H), 5.02- 4.97 (m, 1H), 4.02- 3.39 (m, 2H), 1.39- 1.33 (m, 2H), 1.04- 0.92 (m, 2H) P513 590.1 (300 MHz, DMSO-d₆) δ 3417, 2925, ([M − H]⁻) 8.95 (bs, 1H), 8.20- 2237, 1667, 8.18 (m, 1H), 8.10 (bs, 1162, 565 1H), 8.00-7.90 (m, 2H), 7.67-7.60 (m, 3H), 6.99 (dd, J = 15.6, 9.0 Hz, 1H), 6.77 (d, J = 15.9 Hz, 1H), 4.89- 4.82 (m, 1H), 3.96- 3.91 (m, 2H), 1.40- 1.36 (m, 2H) 1.14-1.09 (m, 2H) P515 582.31 (300 MHz, DMSO-d₆) δ 3392, 2928, ([M + H]⁺) 9.01 (bs, 1H), 8.21- 2239, 1671 8.19 (m, 1H), 8.10 (d, J = 7.2 Hz, 1H), 8.01- 7.94 (m, 2H), 7.89- 7.86 (m, 2H), 7.67- 7.61 (m, 1H), 7.09 (dd, J = 15.9, 9.0 Hz, 1H), 6.89 (d, J = 15.9 Hz, 1H), 4.91-4.85 (m, 1H), 3.95-3.87 (m, 2H), 1.39-1.35 (m, 2H) 1.19-1.08 (m, 2H) P693 580.90 (300 MHz, DMSO-d₆) δ 3280, 2927, ([M + H]⁺) 8.94 (s, 1H), 8.12 (t, J = 1671, 1163, 6.3 Hz, 1H), 7.86 (s, 564 1H), 7.66-7.57 (m, 2H), 7.46-7.38 (m, 2H), 7.22-7.18 (m, 1H), 6.91 (dd, J = 15.6, 8.7 Hz, 1H), 6.74 (d, J = 15.6 Hz, 1H), 4.66-4.60 (m, 1H), 3.99-3.87 (m, 2H), 2.25 (s, 3H), 1.40- 1.33 (m, 2H), 1.11- 1.07 (m, 2H) P1003 701.0 (300 MHz, DMSO-d₆) δ 3422, 1666, ([M + H]⁺) 8.95 (s, 1H), 8.14 (t, J = 1162, 749, 6.3 Hz, 1H), 7.95-7.92 519 (m, 3H), 7.67 (d, J = 7.8 Hz, 1H), 7.60 (d, J = 6.6 Hz, 1H), 7.04 (dd, J = 15.0 Hz, 9.0 Hz, 1H), 6.78 (d, J = 15.6 Hz, 1H), 4.87-4.80 (m, 1H), 3.96-3.91 (m, 2H), 1.39-1.33 (m, 2H), 1.09-1.07 (m, 2H) P1005 151- 690.7 (300 MHz, DMSO-d₆) δ 155 ([M + H]⁺) 9.0 (s, 1H), 8.11 (t, J = 6.6 Hz, 1H), 7.98 (d, J = 6.9 Hz, 2H), 7.92-7.89 (m, 2H), 7.76 (s, 1H), 7.13 (dd, J = 15.9 Hz, 10.5 Hz, 1H), 6.90 (d, J = 15.9 Hz, 1H), 4.94- 4.91 (m, 1H), 3.95- 3.90 (m, 2H), 1.39- 1.37 (m, 2H), 1.01- 1.00 (m, 2H) P1009 666.80 (400 MHz, DMSO-d₆) δ 3428, 2924, ([M + H]⁺) 9.63 (bs, 1H), 9.00 (s, 1113, 743 1H), 7.93 (s, 2H), 7.90 (s, 1H), 7.66-7.59 (m, 2H), 7.00 (dd, J = 16.0, 9.6 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.86- 4.81 (m, 1H), 4.62- 4.58 (m, 2H), 1.35- 1.22 (m, 4H) P1010 622.97 (400 MHz, DMSO-d₆) δ 3401, 1672, ([M + H]⁺) 9.66 (bs, 1H), 9.01 (s, 1171, 806 1H), 7.90 (s, 2H), 7.78 (s, 1H), 7.67-7.58 (m, 2H), 7.01 (dd, J = 16.0, 9.6 Hz, 1H), 6.78 (d, J = 15.6 Hz, 1H), 4.84- 4.82 (m, 1H), 4.61- 4.57 (m, 2H), 1.35-1.29 (m, 4H) P1011 602.94 (300 MHz, DMSO-d₆) δ 3401, 1672, ([M + H]⁺) 9.83 (bs, 1H), 8.76 (s, 1171, 806 1H), 7.90 (s, 2H), 7.72 (d, J = 8.4 Hz, 1H), 7.54- 7.40 (m, 2H), 6.89 (dd, J = 15.3, 8.7 Hz, 1H), 6.75 (d, J = 15.9 Hz, 1H), 4.86-4.80 (m, 1H), 4.54-4.52 (m, 2H), 2.36 (s, 3H), 1.35- 1.28 (m, 4H) P1015 116- 623.0 (300 MHz, DMSO-d₆) δ 120 ([M + H]⁺) 9.01 (bs, 1H), 7.99 (s, 1H), 7.99-7.86 (m, 5H), 7.10 (dd, J = 15.6, 8.6 Hz, 1H), 6.89 (d, J = 15.6 Hz, 1H), 6.18- 5.81 (m, 1H), 4.89- 4.83 (m, 1H), 3.58- 3.31 (m, 2H), 1.38- 1.34 (m, 2H), 1.00- 0.96 (m, 2H) P1020 108- 605.0 (300 MHz, DMSO-d₆) δ 112 ([M + H]⁺) 8.96 (bs, 1H), 7.99 (s, 1H), 7.92-7.85 (m, 4H), 7.69 (bs, 1H), 7.10 (dd, J = 15.9, 8.7 Hz, 1H), 6.89 (d, J = 15.9 Hz, 1H), 4.85-4.83 (m, 1H), 4.51 (t, J = 5.7 Hz, 1H), 4.35 (t, J = 5.1 Hz, 1H), 3.50-3.31 (m, 2H), 1.36-1.23 (m, 2H), 0.98-0.85 (m, 2H) P1023 596.83 (300 MHz, DMSO-d₆) δ 3254, 1666, ([M + H]⁺) 8.86 (bs, 1H), 7.95 (s, 1165 1H), 7.91 (s, 2H), 7.65- 7.61 (m, 2H), 7.50 (d, J = 5.7 Hz, 1H), 6.97 (dd, J = 15.6, 6.6 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.83-4.81 (m, 1H), 3.17-3.10 (m, 2H), 1.33-1.30 (m, 2H), 1.05-1.00 (m, 5H) P1025 586.90 (300 MHz, DMSO-d₆) δ 3448, 2926, ([M + H]⁺) 8.93 (s, 1H), 7.99 (s, 1663, 1114, 1H), 7.95-7.85 (m, 700 4H), 7.47 (t, J = 5.7 Hz, 1H), 7.10 (dd, J = 15.6, 9.0 Hz, 1H), 6.89 (d, J = 15.9 Hz, 1H), 4.89- 4.83 (m, 1H), 3.19- 3.10 (m, 2H), 1.33- 1.29 (m, 2H), 1.05- 1.00 (m, 3H), 0.95- 0.91 (m, 2H) P1026 532.91 (300 MHz, DMSO-d₆) δ 3337, 1651, ([M + H]⁺) 8.68 (s, 1H), 7.89 (s, 1167, 808 1H), 7.63-7.59 (m, 1H), 7.53-7.38 (m, 4H), 6.88 (dd, J = 15.9, 9.0 Hz, 1H), 6.75 (d, J = 15.9 Hz, 1H), 4.85- 4.79 (m, 1H), 3.19- 3.07 (m, 2H), 2.34 (s, 3H), 1.33-1.28 (m, 2H), 1.02-0.90 (m, 5H) P1033 88-91 662.8 (300 MHz, DMSO-d₆) δ ([M + H]⁺) 8.90 (bs, 1H), 7.90- 7.88 (m, 3H), 7.75 (bs, 1H), 7.66-7.59 (m, 2H), 7.01 (dd, J = 15.3, 8.7 Hz, 1H), 6.77 (d, J = 15.6 Hz, 1H), 4.86- 4.80 (m, 1H), 3.40- 3.33 (m, 2H), 2.43- 2.38 (m, 2H), 1.36- 1.32 (m, 2H), 1.04- 1.00 (m, 2H) P1035 89-93 654.9 (300 MHz, DMSO-d₆) δ ([M + H]⁺) 8.98 (bs, 1H), 7.99- 7.85 (m, 5H), 7.77 (bs, 1H), 7.10 (dd, J = 15.9, 8.7 Hz, 1H), 6.89 (d, J = 16.2 Hz, 1H), 4.89- 4.82 (m, 1H), 3.25- 3.18 (m, 2H), 2.44- 2.36 (m, 2H), 1.35- 1.31 (m, 2H), 0.95- 0.92 (m, 2H) P1043 667.0 (300 MHz, DMSO-d₆) δ 3421, 1661, ([M + H]⁺) 8.94 (s, 1H), 8.09 (s, 1163, 802, 1H), 7.91 (s, 1H), 7.71- 516 7.57 (m, 5H), 6.94 (dd, J = 15.6, 9.6 Hz, 1H), 6.78 (d, J = 15.3 Hz, 1H), 4.92-4.70 (m, 1H), 3.96-3.91 (m, 2H), 1.42-1.36 (m, 2H), 1.12-1.07 (m, 2H) P1045 657.2 (400 MHz, DMSO-d₆) δ 3324, 1659, ([M + H]⁺) 9.02 (d, J = 6.4 Hz, 1H), 1146, 679 8.09 (t, J = 6.4 Hz, 1H), 8.10 (d, J = 11.6 Hz, 1H), 7.93-7.86 (m, 2H), 7.73 (d, J = 1.6 Hz, 1H), 7.67 (m, 2H), 7.13 (dd, J = 14.4, Hz, 1H), 6.92 (d, J = 8.0 Hz, 1H) 5.01-4.95 (m, 1H), 3.95-3.88 (m, 2H), 1.38- 1.36 (m, 2H), 1.18- 1.00 (m, 2H) P1048 617.0 (300 MHz, DMSO-d₆) δ 3421.677, ([M + H]⁺) 8.94 (s, 1H), 8.09 (t, J = 1661, 1163, 6.6 Hz, 1H), 7.67-7.56 749, 509 (m, 5H), 7.00 (dd, J = 15.9, 9.3 Hz, 1H), 6.77 (d, J = 15.3 Hz, 1H), 6.58 (s, 1H), 4.83-4.73 (m, 1H), 3.99-3.81 (m, 2H), 1.38-1.36 (m, 2H) 1.17-1.07 (m, 2H) P1050 607.19 (300 MHz, DMSO-d₆) δ 3445, 1668, ([M + H]⁺) 9.01 (s, 1H), 8.10 (t, J = 1166, 802 6.3 Hz, 1H), 8.00 (s, 1H), 7.93-7.86 (m, 2H), 7.69 (m, 3H), 7.10 (dd, J = 15.6, 9.0 Hz, 1H), 6.89 (d, J = 15.6 Hz, 1H), 4.86 (m, 1H), 3.96-3.90 (m, 2H), 1.39-1.33 (m, 2H), 1.03-1.00 (m, 2H) P1093 618.0 (400 MHz, DMSO-d₆) δ 3275, 1668, ([M + H]⁺) 8.94 (s, 1H), 8.10 (t, J = 1163, 749 6.4 Hz, 1H), 7.90-7.87 (m, 2H), 7.73 (d, J = 8.4 Hz, 1H), 7.66-7.60 (m, 2H), 7.56 (d, J = 6.8 Hz, 1H), 6.96 (dd, J = 15.6, 8.8 Hz, 1H), 6.75 (d, J = 15.6 Hz, 1H), 4.82- 4.78 (m, 1H), 3.98- 3.89 (m, 2H), 1.39- 1.36 (m, 2H), 1.10- 1.07 (m, 2H) P1095 607.0 (400 MHz, DMSO-d₆) δ 3459, 1673, ([M + H]⁺) 9.02 (s, 1H), 8.11 (t, J = 1164, 749 5.6 Hz, 1H), 7.97 (s, 1H), 7.93-7.89 (m, 3H), 7.74 (d, J = 8.0 Hz, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.06 (dd, J = 15.6, 8.8 Hz, 1H), 6.87 (d, J = 15.6 Hz, 1H), 4.85 (m, 1H), 3.95-3.90 (m, 2H), 1.37-1.37 (m, 2H), 1.01-1.0 (m, 2H) P1183 706.55 (300 MHz, DMSO-d₆) δ 3289, 1665, ([M + 2]⁺) 8.94 (s, 1H), 8.10 (t, J = 1163, 532 6.0 Hz, 1H), 7.92 (s, 1H), 7.89-7.88 (m, 1H), 7.84 (s, 2H), 7.67- 7.60 (m, 2H), 7.00 (dd, J = 15.6, 9.0 Hz, 1H), 6.76 (d, J = 15.6 Hz, 1H), 4.82-4.76 (m, 1H), 3.99-3.88 (m, 2H), 1.40-1.36 (m, 2H), 1.13-1.07 (m, 2H) P1198 694.99 (400 MHz, DMSO-d₆) δ 3289, 1672, ([M + H]⁺) 9.01 (s, 1H), 8.10 (t, J = 1164, 531 6.4 Hz, 1H), 7.99 (s, 1H), 7.94-7.85 (m, 5H), 7.09 (dd, J = 15.6, 8.8 Hz, 1H), 6.88 (d, J = 15.6 Hz, 1H), 4.85- 4.80 (m, 1H), 3.95- 3.88 (m, 2H), 1.39- 1.33 (m, 2H), 1.02- 0.99 (m, 2H) P1193 80-83 687.00 (300 MHz, DMSO-d₆) δ ([M + H]⁺) 8.94 (bs, 1H), 7.97- 7.84 (m, 5H), 7.66- 7.60 (m, 2H), 6.99 (dd, J = 15.6, 9.2 Hz, 1H), 6.76 (d, J = 15.6 Hz, 1H), 6.14-5.86 (m, 1H), 4.81-4.76 (m, 1H), 3.59-3.49 (m, 2H), 1.38-1.35 (m, 2H), 1.08-1.06 (m, 2H) P1195 676.65 (300 MHz, DMSO-d₆) δ 3414, 1664, ([M + H]⁺) 9.00 (bs, 1H), 7.99 (bs, 1114, 537 1H), 7.94-7.85 (m, 5H), 7.10 (dd, J = 15.6, 8.7 Hz, 1H), 6.88 (d, J = 15.6 Hz, 1H), 6.18- 5.81 (m, 1H), 4.84- 4.74 (m, 1H), 3.58- 3.46 (m, 2H), 1.38- 1.35 (m, 2H), 0.99- 0.96 (m, 2H) P1200 659.35 (300 MHz, DMSO-d₆) δ 3450, 1659, ([M + H]⁺) 8.98 (bs, 1H), 7.99 1115, 559 (s, 1H), 7.89-7.85 (m, 5H), 7.69 (bs, 1H), 7.05 (dd, J = 15.9, 9.2 Hz, 1H), 6.88 (d, J = 15.9 Hz, 1H), 4.84-4.76 (m, 1H), 4.51-4.49 (m, 1H), 4.37-4.35 (m, 1H), 3.48-3.35 (m, 2H), 1.33-1.32 (m, 2H), 0.96-0.95 (m, 2H) P1213 716.70 (300 MHz, DMSO-d₆) δ 3241, 1659, ([M − H]⁺) 8.89 (bs, 1H), 7.92- 1159, 554 7.88 (m, 2H), 7.84 (s, 2H), 7.77 (bs, 1H), 7.63- 7.62 (m, 2H), 7.00 (dd, J = 15.9, 9.2 Hz, 1H), 6.76 (d, J = 15.6 Hz, 1H), 4.84-4.75 (m, 1H), 3.40-3.36 (m, 2H), 2.42-2.38 (m, 2H), 1.36-1.32 (m, 2H), 1.04-1.00 (m, 2H) ^(a1)H NMR spectral data were acquired using a 400 MHz instrument in CDCl₃ except where noted. HRMS data are noted observed value (theoretical value).

TABLE 3 Assays Results Part 1 Compound BAW CEW GPA Number Rating Rating Rating AC1 D D B AC2 C C C AC3 D D B AC4 D A B AC5 D D B AC6 D A B AC7 A A B AC8 D B B AC9 A A B AC10 A A B AC11 A A D AC12 A A D AC13 A A B AC14 A B D AC15 A A B AC16 A A C AC17 A A B AC18 A A B AC19 D D B AC20 A A C AC21 D D C AC22 A A D AC23 A A B AC24 A A D AC25 A A D AC26 A A B AC27 A A B AC28 A A B AC29 A A B AC30 A A B AC31 A A B AC32 A A B AC33 A A B AC34 A A B AC35 A A C AC36 A A B AC37 A A B AC38 A A C AC39 A A C AC40 A A D AC41 A D D AC42 A D D AC43 A A B AC44 A A B AC45 A A D AC46 A A D AC47 D D B AC48 A A B AC49 A A B AC50 A D B AC51 A A B AC52 A A B AC53 A A B AC54 A A B AC57 A A B AC58 A A B AC59 A A B AC60 A A B AC61 A A B AC62 A A D AC63 A A B AC64 A A B AC65 A A B AC66 A A B AC67 A A B AC68 A A D AC69 A A A AC70 D D B AC71 A A B AC72 A A B AC75 A A B AC76 A A D AC77 A A B AC78 A A A AC79 A A A AC80 A A B AC81 A D D AC82 A A B AC83 A A B AC84 A A D AC85 A A B AC86 A A D AC87 A A B AC89 A A B AC90 A A C AC91 A A C AC92 A A C AC93 A D C AC94 D B B AC95 A A C AC96 D D C AC97 D D C AC98 A A C AC99 A A C AC100 C C C AC101 D D C AC102 D A C AC103 A A D AC104 A A B AC105 A A D AC106 A A B AC107 B A D AC108 B D D AC109 D D C AC110 A A C AC111 A A C AC112 A A C AC113 B A D AC114 A B D AC115 A A D AC116 C C C AC117 A D B AC118 A D D BC1 A A D BC2 A A D BC3 A A D BC4 A A B BC5 A A B BC6 A A D BC7 A A D BC8 A A B BC9 A A D BC10 A A B BC11 C C C BC12 C C C BC13 A A D BC14 A D D CC1 D D D CC2 A A B CC3 A A D CC4 A B B CC5 A A B CC6 A A B CC7 A A B CC8 A A D CC9 A A B CC10 A A B CC11 A A B CC12 D D B CC13 A A B CC14 A D D CC15 A A B CC16 A A B CC17 A A B CC18 A A B CC19 A A B CC20 A A D CC21 A A D CC22 A A B CC23 A A B CC24 A A D CC25 A A B CC26 A D B CC27 A A D CC28 A A D CC29 A A B CC30 A A D CC31 B D C CC32 A A B CC33 A A B CC34 A A B CC35 D D D CC36 A A D CC37 A A D CC38 A A D CC39 D D B CC40 D A D CC41 D D B CC42 D D D CC43 A B B CC44 A A B CC45 A A D CC46 D A C CC47 D D C CC48 D D C CC49 D D D CC50 A A D CC51 A A D CC52 A D D CC53 D D B CC54 A A C DC1 A A D DC2 D D C DC3 B D C DC4 A D C DC5 D D C DC6 D D C DC7 A D C DC8 A D C DC9 D D C DC10 D D C DC11 A D C DC12 A A B DC13 A A C DC14 D D C DC15 D D C DC16 A A C DC17 A A C DC18 A A C DC19 A A C DC20 A D C DC21 D D C DC22 D D C DC23 D A C DC24 D D C DC25 D D C DC26 D D C DC27 D D C DC28 A A B DC29 A A C DC30 A A C DC31 A A B DC32 D D C DC33 A A C DC34 A A B DC35 A A B DC36 D D C DC37 A A C DC38 A A C DC39 A A C DC40 A A C DC41 A A C DC42 A A C DC43 A A C DC44 A A C DC45 A A C DC46 A A C DC47 A A C DC48 A A C DC49 A A C DC50 A A C DC51 A A C DC52 D D C DC53 D A C DC54 D D C DC55 D D C DC56 D D C DC57 A A C DC58 D D C DC59 D D C DC60 A A C DC61 D D C DC62 A A C DC63 A A C DC64 D D C DC65 D A C DC66 A A C DC67 A A C DC68 A A C DC69 D D C DC70 A A C

TABLE 4 Assay Results F Compounds Compound BAW CL GPA Number Rating Rating Rating F1 A A C F2 A A C F3 A A C F4 A A C F5 A A B F6 A A C F7 A A C F8 A A C F8A A A C F8B A A C

TABLE 5 Assay Results Prophetic Compounds Subsequently Exemplified Compound BAW CL GPA Number Rating Rating Rating P31 A A C P65 A A C P108 A A C P110 A A C P153 A A C P155 A A C P198 A A C P200 A A C P243 A A C P245 A A C P333 A A C P335 A A C P336 A A C P378 A A C P380 A A C P423 A A C P425 A A C P468 A A C P470 A A B P513 A A C P515 A A C P693 A A C P1003 A A D P1005 A A C P1009 A A C P1010 A A C P1011 A A C P1015 A A C P1020 A A C P1023 A A C P1025 A A B P1026 A A B P1033 A A C P1035 A A C P1043 A A C P1045 A A C P1048 A A C P1050 A A C P1093 A A C P1095 A A C P1183 A A C P1198 A A C P1193 A A C P1195 A A C P1200 A A C P1213 A A C 

We claim:
 1. A composition comprising a molecule according to Formula One:

wherein: (a) R1 is selected from the group consisting of H and Cl; (b) R2 is selected from the group consisting of H, F, Cl, Br, and (C₁-C₈)alkyl; (c) R3 is selected from the group consisting of H, F, Cl, and Br; (d) R4 is selected from the group consisting of F, Cl, Br, CN, NO₂, (C₁-C₈)alkyl, and halo(C₁-C₈)alkyl; (e) R5 is selected from the group consisting of H and F; (f) R6 is a (C₁-C₈)haloalkyl; (g) R7 is H; (h) R8 is H; (i) R9 is H; (j) R10 is selected from the group consisting of Cl, Br, (C₁-C₈)alkyl, and halo(C₁-C₈)alkyl; (k) R11 is C(═X5)N(X6)(R14), wherein X5 is selected from the group consisting of O and S, and X6 is selected from the group consisting of halocyclo(C₃-C₆)alkyl and substituted cyclo(C₃-C₆)alkyl wherein said substituted cyclo(C₃-C₆)alkyl is substituted with one or more substituents selected from the group consisting of CN and C(═X5)N(R15)(R16); (l) R12 is H; (m) R13 is H; (n) R14 is H; (o) R15 is H; (p) R16 is selected from the group consisting of (C₁-C₈)alkyl and halo(C₁-C₈)alkyl; (r) X1 is CR12; (s) X2 is CR13; and (t) X3 is CR9.
 2. A composition according to claim 1 wherein said molecule said R2 is selected from the group consisting of H, F, Cl, Br, and CH₃.
 3. A composition according to claim 1 wherein said molecule said R4 is selected from the group consisting of F, Cl, Br, CN, NO₂, CH₃, and OCF₃.
 4. A composition according to claim 1 wherein said molecule said R6 is selected from the group consisting of halomethyl, and haloethyl.
 5. A composition according to claim 1 wherein said molecule said R6 is trifluoromethyl or pentafluoroethyl.
 6. A composition according to claim 1 wherein said molecule said R10 is selected from the group consisting of Cl, Br, CH₃, and CF₃.
 7. A composition according to claim 1 wherein said molecule said R11 is selected from the group consisting of (C═O)N(H)(cyclopropyl-(C═O)N(H)(CH₂CF₃)), (C═O)N(H)(cyclopropyl-(C═O)N(H)(CH₂CH₂CF₃)), (C═O)N(H)(cyclopropyl-(C═O)N(H)(CH₂CH₂F)), (C═O)N(H)(cyclopropyl-(C═O)N(H)(CH₂CH₃)), (C═O)N(H)(cyclopropyl-(C═O)N(H)(CH₂CHF₂)), (C═O)N(H)(cyclopropyl-(C═S)N(H)(CH₂CF₃)), (C═O)N(H)(cyclobutyl-(C═O)N(H)(CH₂CF₃)), (C═O)N(H)(cyclopropyl-CN), and (C═O)N(H)(difluorocyclopropyl).
 8. A composition according to claim 1 wherein said molecule said R11 is selected from the group consisting of (C═(O)N(H)(cyclopropyl-(C═(O or S))N(H)(halo(C₁-C₆)alkyl)), (C═(O)N(H)(cyclobutyl-(C═(O))N(H)(halo(C₁-C₆)alkyl)), and (C═(O)N(H)(cyclopropyl-(C═(O))N(H)((C₁-C₆)alkyl)).
 9. A composition according to claim 1 wherein said molecule said R16 is selected from the group consisting of methyl, ethyl, halomethyl, haloethyl, and halo(C₃)alkyl.
 10. A composition according to claim 1 wherein said molecule said R16 is selected from the group consisting of CH₂CH₃, CH₂CF₃, CH₂CHF₂, CH₂CH₂F, and CH₂CH₂CF₃.
 11. A composition according to claim 1 further comprising: (a) one or more compounds having acaricidal, algicidal, avicidal, bactericidal, fungicidal, herbicidal, insecticidal, molluscicidal, nematicidal, rodenticidal, or virucidal properties; or (b) one or more compounds that are antifeedants, bird repellents, chemosterilants, herbicide safeners, insect attractants, insect repellents, mammal repellents, mating disrupters, plant activators, plant growth regulators, or synergists; or (c) both (a) and (b).
 12. A composition according to claim 1 further comprising one or more compounds selected from the group consisting of: (3-ethoxypropyl)mercury bromide, 1,2-dichloropropane, 1,3-dichloropropene, 1-methylcyclopropene, 1-naphthol, 2-(octylthio)ethanol, 2,3,5-tri-iodobenzoic acid, 2,3,6-TBA, 2,3,6-TBA-dimethylammonium, 2,3,6-TBA-lithium, 2,3,6-TBA-potassium, 2,3,6-TBA-sodium, 2,4,5-T, 2,4,5-T-2-butoxypropyl, 2,4,5-T-2-ethylhexyl, 2,4,5-T-3-butoxypropyl, 2,4,5-TB, 2,4,5-T-butometyl, 2,4,5-T-butotyl, 2,4,5-T-butyl, 2,4,5-T-isobutyl, 2,4,5-T-isoctyl, 2,4,5-T-isopropyl, 2,4,5-T-methyl, 2,4,5-T-pentyl, 2,4,5-T-sodium, 2,4,5-T-triethylammonium, 2,4,5-T-trolamine, 2,4-D, 2,4-D-2-butoxypropyl, 2,4-D-2-ethylhexyl, 2,4-D-3-butoxypropyl, 2,4-D-ammonium, 2,4-DB, 2,4-DB-butyl, 2,4-DB-dimethylammonium, 2,4-DB-isoctyl, 2,4-DB-potassium, 2,4-DB-sodium, 2,4-D-butotyl, 2,4-D-butyl, 2,4-D-diethylammonium, 2,4-D-dimethylammonium, 2,4-D-diolamine, 2,4-D-dodecylammonium, 2,4-DEB, 2,4-DEP, 2,4-D-ethyl, 2,4-D-heptylammonium, 2,4-D-isobutyl, 2,4-D-isoctyl, 2,4-D-isopropyl, 2,4-D-isopropylammonium, 2,4-D-lithium, 2,4-D-meptyl, 2,4-D-methyl, 2,4-D-octyl, 2,4-D-pentyl, 2,4-D-potassium, 2,4-D-propyl, 2,4-D-sodium, 2,4-D-tefuryl, 2,4-D-tetradecylammonium, 2,4-D-triethylammonium, 2,4-D-tris(2-hydroxypropyl)ammonium, 2,4-D-trolamine, 2iP, 2-methoxyethylmercury chloride, 2-phenylphenol, 3,4-DA, 3,4-DB, 3,4-DP, 4-aminopyridine, 4-CPA, 4-CPA-potassium, 4-CPA-sodium, 4-CPB, 4-CPP, 4-hydroxyphenethyl alcohol, 8-hydroxyquinoline sulfate, 8-phenylmercurioxyquinoline, abamectin, abscisic acid, ACC, acephate, acequinocyl, acetamiprid, acethion, acetochlor, acetophos, acetoprole, acibenzolar, acibenzolar-S-methyl, acifluorfen, acifluorfen-methyl, acifluorfen-sodium, aclonifen, acrep, acrinathrin, acrolein, acrylonitrile, acypetacs, acypetacs-copper, acypetacs-zinc, alachlor, alanycarb, albendazole, aldicarb, aldimorph, aldoxycarb, aldrin, allethrin, allicin, allidochlor, allosamidin, alloxydim, alloxydim-sodium, allyl alcohol, allyxycarb, alorac, alpha-cypermethrin, alpha-endosulfan, ametoctradin, ametridione, ametryn, amibuzin, amicarbazone, amicarthiazol, amidithion, amidoflumet, amidosulfuron, aminocarb, aminocyclopyrachlor, aminocyclopyrachlor-methyl, aminocyclopyrachlor-potassium, aminopyralid, aminopyralid-potassium, aminopyralid-tris(2-hydroxypropyl)ammonium, amiprofos-methyl, amiprophos, amisulbrom, amiton, amiton oxalate, amitraz, amitrole, ammonium sulfamate, ammonium α-naphthaleneacetate, amobam, ampropylfos, anabasine, ancymidol, anilazine, anilofos, anisuron, anthraquinone, antu, apholate, aramite, arsenous oxide, asomate, aspirin, asulam, asulam-potassium, asulam-sodium, athidathion, atraton, atrazine, aureofungin, aviglycine, aviglycine hydrochloride, azaconazole, azadirachtin, azafenidin, azamethiphos, azimsulfuron, azinphos-ethyl, azinphos-methyl, aziprotryne, azithiram, azobenzene, azocyclotin, azothoate, azoxystrobin, bachmedesh, barban, barium hexafluorosilicate, barium polysulfide, barthrin, BCPC, beflubutamid, benalaxyl, benalaxyl-M, benazolin, benazolin-dimethylammonium, benazolin-ethyl, benazolin-potassium, bencarbazone, benclothiaz, bendiocarb, benfluralin, benfuracarb, benfuresate, benodanil, benomyl, benoxacor, benoxafos, benquinox, bensulfuron, bensulfuron-methyl, bensulide, bensultap, bentaluron, bentazone, bentazone-sodium, benthiavalicarb, benthiavalicarb-isopropyl, benthiazole, bentranil, benzadox, benzadox-ammonium, benzalkonium chloride, benzamacril, benzamacril-isobutyl, benzamorf, benzfendizone, benzipram, benzobicyclon, benzofenap, benzofluor, benzohydroxamic acid, benzoximate, benzoylprop, benzoylprop-ethyl, benzthiazuron, benzyl benzoate, benzyladenine, berberine, berberine chloride, beta-cyfluthrin, beta-cypermethrin, bethoxazin, bicyclopyrone, bifenazate, bifenox, bifenthrin, bifujunzhi, bilanafos, bilanafos-sodium, binapacryl, bingqingxiao, bioallethrin, bioethanomethrin, biopermethrin, bioresmethrin, biphenyl, bisazir, bismerthiazol, bispyribac, bispyribac-sodium, bistrifluron, bitertanol, bithionol, bixafen, blasticidin-S, borax, Bordeaux mixture, boric acid, boscalid, brassinolide, brassinolide-ethyl, brevicomin, brodifacoum, brofenvalerate, brofluthrinate, bromacil, bromacil-lithium, bromacil-sodium, bromadiolone, bromethalin, bromethrin, bromfenvinfos, bromoacetamide, bromobonil, bromobutide, bromocyclen, bromo-DDT, bromofenoxim, bromophos, bromophos-ethyl, bromopropylate, bromothalonil, bromoxynil, bromoxynil butyrate, bromoxynil heptanoate, bromoxynil octanoate, bromoxynil-potassium, brompyrazon, bromuconazole, bronopol, bucarpolate, bufencarb, buminafos, bupirimate, buprofezin, Burgundy mixture, busulfan, butacarb, butachlor, butafenacil, butamifos, butathiofos, butenachlor, butethrin, buthidazole, buthiobate, buthiuron, butocarboxim, butonate, butopyronoxyl, butoxycarboxim, butralin, butroxydim, buturon, butylamine, butylate, cacodylic acid, cadusafos, cafenstrole, calcium arsenate, calcium chlorate, calcium cyanamide, calcium polysulfide, calvinphos, cambendichlor, camphechlor, camphor, captafol, captan, carbamorph, carbanolate, carbaryl, carbasulam, carbendazim, carbendazim benzenesulfonate, carbendazim sulfite, carbetamide, carbofuran, carbon disulfide, carbon tetrachloride, carbophenothion, carbosulfan, carboxazole, carboxide, carboxin, carfentrazone, carfentrazone-ethyl, carpropamid, cartap, cartap hydrochloride, carvacrol, carvone, CDEA, cellocidin, CEPC, ceralure, Cheshunt mixture, chinomethionat, chitosan, chlobenthiazone, chlomethoxyfen, chloralose, chloramben, chloramben-ammonium, chloramben-diolamine, chloramben-methyl, chloramben-methylammonium, chloramben-sodium, chloramine phosphorus, chloramphenicol, chloraniformethan, chloranil, chloranocryl, chlorantraniliprole, chlorazifop, chlorazifop-propargyl, chlorazine, chlorbenside, chlorbenzuron, chlorbicyclen, chlorbromuron, chlorbufam, chlordane, chlordecone, chlordimeform, chlordimeform hydrochloride, chlorempenthrin, chlorethoxyfos, chloreturon, chlorfenac, chlorfenac-ammonium, chlorfenac-sodium, chlorfenapyr, chlorfenazole, chlorfenethol, chlorfenprop, chlorfenson, chlorfensulphide, chlorfenvinphos, chlorfluazuron, chlorflurazole, chlorfluren, chlorfluren-methyl, chlorflurenol, chlorflurenol-methyl, chloridazon, chlorimuron, chlorimuron-ethyl, chlormephos, chlormequat, chlormequat chloride, chlornidine, chlornitrofen, chlorobenzilate, chlorodinitronaphthalenes, chloroform, chloromebuform, chloromethiuron, chloroneb, chlorophacinone, chlorophacinone-sodium, chloropicrin, chloropon, chloropropylate, chlorothalonil, chlorotoluron, chloroxuron, chloroxynil, chlorphonium, chlorphonium chloride, chlorphoxim, chlorprazophos, chlorprocarb, chlorpropham, chlorpyrifos, chlorpyrifos-methyl, chlorquinox, chlorsulfuron, chlorthal, chlorthal-dimethyl, chlorthal-monomethyl, chlorthiamid, chlorthiophos, chlozolinate, choline chloride, chromafenozide, cinerin I, cinerin II, cinerins, cinidon-ethyl, cinmethylin, cinosulfuron, ciobutide, cisanilide, cismethrin, clethodim, climbazole, cliodinate, clodinafop, clodinafop-propargyl, cloethocarb, clofencet, clofencet-potassium, clofentezine, clofibric acid, clofop, clofop-isobutyl, clomazone, clomeprop, cloprop, cloproxydim, clopyralid, clopyralid-methyl, clopyralid-olamine, clopyralid-potassium, clopyralid-tris(2-hydroxypropyl)ammonium, cloquintocet, cloquintocet-mexyl, cloransulam, cloransulam-methyl, closantel, clothianidin, clotrimazole, cloxyfonac, cloxyfonac-sodium, CMA, codlelure, colophonate, copper acetate, copper acetoarsenite, copper arsenate, copper carbonate, basic, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper silicate, copper sulfate, copper zinc chromate, coumachlor, coumafuryl, coumaphos, coumatetralyl, coumithoate, coumoxystrobin, CPMC, CPMF, CPPC, credazine, cresol, crimidine, crotamiton, crotoxyphos, crufomate, cryolite, cue-lure, cufraneb, cumyluron, cuprobam, cuprous oxide, curcumenol, cyanamide, cyanatryn, cyanazine, cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyazofamid, cybutryne, cyclafuramid, cyclanilide, cyclethrin, cycloate, cycloheximide, cycloprate, cycloprothrin, cyclosulfamuron, cycloxaprid, cycloxydim, cycluron, cyenopyrafen, cyflufenamid, cyflumetofen, cyfluthrin, cyhalofop, cyhalofop-butyl, cyhalothrin, cyhexatin, cymiazole, cymiazole hydrochloride, cymoxanil, cyometrinil, cypendazole, cypermethrin, cyperquat, cyperquat chloride, cyphenothrin, cyprazine, cyprazole, cyproconazole, cyprodinil, cyprofuram, cypromid, cyprosulfamide, cyromazine, cythioate, daimuron, dalapon, dalapon-calcium, dalapon-magnesium, dalapon-sodium, daminozide, dayoutong, dazomet, dazomet-sodium, DBCP, d-camphor, DCIP, DCPTA, DDT, debacarb, decafentin, decarbofuran, dehydroacetic acid, delachlor, deltamethrin, demephion, demephion-O, demephion-S, demeton, demeton-methyl, demeton-O, demeton-O-methyl, demeton-S, demeton-S-methyl, demeton-S-methylsulphon, desmedipham, desmetryn, d-fanshiluquebingjuzhi, diafenthiuron, dialifos, di-allate, diamidafos, diatomaceous earth, diazinon, dibutyl phthalate, dibutyl succinate, dicamba, dicamba-diglycolamine, dicamba-dimethylammonium, dicamba-diolamine, dicamba-isopropylammonium, dicamba-methyl, dicamba-olamine, dicamba-potassium, dicamba-sodium, dicamba-trolamine, dicapthon, dichlobenil, dichlofenthion, dichlofluanid, dichlone, dichloralurea, dichlorbenzuron, dichlorflurenol, dichlorflurenol-methyl, dichlormate, dichlormid, dichlorophen, dichlorprop, dichlorprop-2-ethylhexyl, dichlorprop-butotyl, dichlorprop-dimethylammonium, dichlorprop-ethylammonium, dichlorprop-isoctyl, dichlorprop-methyl, dichlorprop-P, dichlorprop-P-2-ethylhexyl, dichlorprop-P-dimethylammonium, dichlorprop-potassium, dichlorprop-sodium, dichlorvos, dichlozoline, diclobutrazol, diclocymet, diclofop, diclofop-methyl, diclomezine, diclomezine-sodium, dicloran, diclosulam, dicofol, dicoumarol, dicresyl, dicrotophos, dicyclanil, dicyclonon, dieldrin, dienochlor, diethamquat, diethamquat dichloride, diethatyl, diethatyl-ethyl, diethofencarb, dietholate, diethyl pyrocarbonate, diethyltoluamide, difenacoum, difenoconazole, difenopenten, difenopenten-ethyl, difenoxuron, difenzoquat, difenzoquat metilsulfate, difethialone, diflovidazin, diflubenzuron, diflufenican, diflufenzopyr, diflufenzopyr-sodium, diflumetorim, dikegulac, dikegulac-sodium, dilor, dimatif, dimefluthrin, dimefox, dimefuron, dimepiperate, dimetachlone, dimetan, dimethacarb, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimethipin, dimethirimol, dimethoate, dimethomorph, dimethrin, dimethyl carbate, dimethyl phthalate, dimethylvinphos, dimetilan, dimexano, dimidazon, dimoxystrobin, dinex, dinex-diclexine, dingjunezuo, diniconazole, diniconazole-M, dinitramine, dinobuton, dinocap, dinocap-4, dinocap-6, dinocton, dinofenate, dinopenton, dinoprop, dinosam, dinoseb, dinoseb acetate, dinoseb-ammonium, dinoseb-diolamine, dinoseb-sodium, dinoseb-trolamine, dinosulfon, dinotefuran, dinoterb, dinoterb acetate, dinoterbon, diofenolan, dioxabenzofos, dioxacarb, dioxathion, diphacinone, diphacinone-sodium, diphenamid, diphenyl sulfone, diphenylamine, dipropalin, dipropetryn, dipyrithione, diquat, diquat dibromide, disparlure, disul, disulfiram, disulfoton, disul-sodium, ditalimfos, dithianon, dithicrofos, dithioether, dithiopyr, diuron, d-limonene, DMPA, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium, dodemorph, dodemorph acetate, dodemorph benzoate, dodicin, dodicin hydrochloride, dodicin-sodium, dodine, dofenapyn, dominicalure, doramectin, drazoxolon, DSMA, dufulin, EBEP, EBP, ecdysterone, edifenphos, eglinazine, eglinazine-ethyl, emamectin, emamectin benzoate, EMPC, empenthrin, endosulfan, endothal, endothal-diammonium, endothal-dipotassium, endothal-disodium, endothion, endrin, enestroburin, EPN, epocholeone, epofenonane, epoxiconazole, eprinomectin, epronaz, EPTC, erbon, ergocalciferol, erlujixiancaoan, esdépalléthrine, esfenvalerate, esprocarb, etacelasil, etaconazole, etaphos, etem, ethaboxam, ethachlor, ethalfluralin, ethametsulfuron, ethametsulfuron-methyl, ethaprochlor, ethephon, ethidimuron, ethiofencarb, ethiolate, ethion, ethiozin, ethiprole, ethirimol, ethoate-methyl, ethofumesate, ethohexadiol, ethoprophos, ethoxyfen, ethoxyfen-ethyl, ethoxyquin, ethoxysulfuron, ethychlozate, ethyl formate, ethyl α-naphthaleneacetate, ethyl-DDD, ethylene, ethylene dibromide, ethylene dichloride, ethylene oxide, ethylicin, ethylmercury 2,3-dihydroxypropyl mercaptide, ethylmercury acetate, ethylmercury bromide, ethylmercury chloride, ethylmercury phosphate, etinofen, etnipromid, etobenzanid, etofenprox, etoxazole, etridiazole, etrimfos, eugenol, EXD, famoxadone, famphur, fenamidone, fenaminosulf, fenamiphos, fenapanil, fenarimol, fenasulam, fenazaflor, fenazaquin, fenbuconazole, fenbutatin oxide, fenchlorazole, fenchlorazole-ethyl, fenchlorphos, fenclorim, fenethacarb, fenfluthrin, fenfuram, fenhexamid, fenitropan, fenitrothion, fenjuntong, fenobucarb, fenoprop, fenoprop-3-butoxypropyl, fenoprop-butometyl, fenoprop-butotyl, fenoprop-butyl, fenoprop-isoctyl, fenoprop-methyl, fenoprop-potassium, fenothiocarb, fenoxacrim, fenoxanil, fenoxaprop, fenoxaprop-ethyl, fenoxaprop-P, fenoxaprop-P-ethyl, fenoxasulfone, fenoxycarb, fenpiclonil, fenpirithrin, fenpropathrin, fenpropidin, fenpropimorph, fenpyrazamine, fenpyroximate, fenridazon, fenridazon-potassium, fenridazon-propyl, fenson, fensulfothion, fenteracol, fenthiaprop, fenthiaprop-ethyl, fenthion, fenthion-ethyl, fentin, fentin acetate, fentin chloride, fentin hydroxide, fentrazamide, fentrifanil, fenuron, fenuron TCA, fenvalerate, ferbam, ferimzone, ferrous sulfate, fipronil, flamprop, flamprop-isopropyl, flamprop-M, flamprop-methyl, flamprop-M-isopropyl, flamprop-M-methyl, flazasulfuron, flocoumafen, flometoquin, flonicamid, florasulam, fluacrypyrim, fluazifop, fluazifop-butyl, fluazifop-methyl, fluazifop-P, fluazifop-P-butyl, fluazinam, fluazolate, fluazuron, flubendiamide, flubenzimine, flucarbazone, flucarbazone-sodium, flucetosulfuron, fluchloralin, flucofuron, flucycloxuron, flucythrinate, fludioxonil, fluenetil, fluensulfone, flufenacet, flufenerim, flufenican, flufenoxuron, flufenprox, flufenpyr, flufenpyr-ethyl, flufiprole, flumethrin, flumetover, flumetralin, flumetsulam, flumezin, flumiclorac, flumiclorac-pentyl, flumioxazin, flumipropyn, flumorph, fluometuron, fluopicolide, fluopyram, fluorbenside, fluoridamid, fluoroacetamide, fluorodifen, fluoroglycofen, fluoroglycofen-ethyl, fluoroimide, fluoromidine, fluoronitrofen, fluothiuron, fluotrimazole, fluoxastrobin, flupoxam, flupropacil, flupropadine, flupropanate, flupropanate-sodium, flupyradifurone, flupyrsulfuron, flupyrsulfuron-methyl, flupyrsulfuron-methyl-sodium, fluquinconazole, flurazole, flurenol, flurenol-butyl, flurenol-methyl, fluridone, flurochloridone, fluroxypyr, fluroxypyr-butometyl, fluroxypyr-meptyl, flurprimidol, flursulamid, flurtamone, flusilazole, flusulfamide, fluthiacet, fluthiacet-methyl, flutianil, flutolanil, flutriafol, fluvalinate, fluxapyroxad, fluxofenim, folpet, fomesafen, fomesafen-sodium, fonofos, foramsulfuron, forchlorfenuron, formaldehyde, formetanate, formetanate hydrochloride, formothion, formparanate, formparanate hydrochloride, fosamine, fosamine-ammonium, fosetyl, fosetyl-aluminium, fosmethilan, fospirate, fosthiazate, fosthietan, frontalin, fuberidazole, fucaojing, fucaomi, funaihecaoling, fuphenthiourea, furalane, furalaxyl, furamethrin, furametpyr, furathiocarb, furcarbanil, furconazole, furconazole-cis, furethrin, furfural, furilazole, furmecyclox, furophanate, furyloxyfen, gamma-cyhalothrin, gamma-HCH, genit, gibberellic acid, gibberellins, gliftor, glufosinate, glufosinate-ammonium, glufosinate-P, glufosinate-P-ammonium, glufosinate-P-sodium, glyodin, glyoxime, glyphosate, glyphosate-diammonium, glyphosate-dimethylammonium, glyphosate-isopropylammonium, glyphosate-monoammonium, glyphosate-potassium, glyphosate-sesquisodium, glyphosate-trimesium, glyphosine, gossyplure, grandlure, griseofulvin, guazatine, guazatine acetates, halacrinate, halfenprox, halofenozide, halosafen, halosulfuron, halosulfuron-methyl, haloxydine, haloxyfop, haloxyfop-etotyl, haloxyfop-methyl, haloxyfop-P, haloxyfop-P-etotyl, haloxyfop-P-methyl, haloxyfop-sodium, HCH, hemel, hempa, HEOD, heptachlor, heptenophos, heptopargil, heterophos, hexachloroacetone, hexachlorobenzene, hexachlorobutadiene, hexachlorophene, hexaconazole, hexaflumuron, hexaflurate, hexalure, hexamide, hexazinone, hexylthiofos, hexythiazox, HHDN, holosulf, huancaiwo, huangcaoling, huanjunzuo, hydramethylnon, hydrargaphen, hydrated lime, hydrogen cyanide, hydroprene, hymexazol, hyquincarb, IAA, IBA, icaridin, imazalil, imazalil nitrate, imazalil sulfate, imazamethabenz, imazamethabenz-methyl, imazamox, imazamox-ammonium, imazapic, imazapic-ammonium, imazapyr, imazapyr-isopropylammonium, imazaquin, imazaquin-ammonium, imazaquin-methyl, imazaquin-sodium, imazethapyr, imazethapyr-ammonium, imazosulfuron, imibenconazole, imicyafos, imidacloprid, imidaclothiz, iminoctadine, iminoctadine triacetate, iminoctadine trialbesilate, imiprothrin, inabenfide, indanofan, indaziflam, indoxacarb, inezin, iodobonil, iodocarb, iodomethane, iodosulfuron, iodosulfuron-methyl, iodosulfuron-methyl-sodium, iofensulfuron, iofensulfuron-sodium, ioxynil, ioxynil octanoate, ioxynil-lithium, ioxynil-sodium, ipazine, ipconazole, ipfencarbazone, iprobenfos, iprodione, iprovalicarb, iprymidam, ipsdienol, ipsenol, IPSP, isamidofos, isazofos, isobenzan, isocarbamid, isocarbophos, isocil, isodrin, isofenphos, isofenphos-methyl, isolan, isomethiozin, isonoruron, isopolinate, isoprocarb, isopropalin, isoprothiolane, isoproturon, isopyrazam, isopyrimol, isothioate, isotianil, isouron, isovaledione, isoxaben, isoxachlortole, isoxadifen, isoxadifen-ethyl, isoxaflutole, isoxapyrifop, isoxathion, ivermectin, izopamfos, japonilure, japothrins, jasmolin I, jasmolin II, jasmonic acid, jiahuangchongzong, jiajizengxiaolin, jiaxiangjunzhi, jiecaowan, jiecaoxi, jodfenphos, juvenile hormone I, juvenile hormone II, juvenile hormone III, kadethrin, karbutilate, karetazan, karetazan-potassium, kasugamycin, kasugamycin hydrochloride, kejunlin, kelevan, ketospiradox, ketospiradox-potassium, kinetin, kinoprene, kresoxim-methyl, kuicaoxi, lactofen, lambda-cyhalothrin, latilure, lead arsenate, lenacil, lepimectin, leptophos, lindane, lineatin, linuron, lirimfos, litlure, looplure, lufenuron, lvdingjunzhi, lvxiancaolin, lythidathion, MAA, malathion, maleic hydrazide, malonoben, maltodextrin, MAMA, mancopper, mancozeb, mandipropamid, maneb, matrine, mazidox, MCPA, MCPA-2-ethylhexyl, MCPA-butotyl, MCPA-butyl, MCPA-dimethylammonium, MCPA-diolamine, MCPA-ethyl, MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl, MCPA-methyl, MCPA-olamine, MCPA-potassium, MCPA-sodium, MCPA-thioethyl, MCPA-trolamine, MCPB, MCPB-ethyl, MCPB-methyl, MCPB-sodium, mebenil, mecarbam, mecarbinzid, mecarphon, mecoprop, mecoprop-2-ethylhexyl, mecoprop-dimethylammonium, mecoprop-diolamine, mecoprop-ethadyl, mecoprop-isoctyl, mecoprop-methyl, mecoprop-P, mecoprop-P-2-ethylhexyl, mecoprop-P-dimethylammonium, mecoprop-P-isobutyl, mecoprop-potassium, mecoprop-P-potassium, mecoprop-sodium, mecoprop-trolamine, medimeform, medinoterb, medinoterb acetate, medlure, mefenacet, mefenpyr, mefenpyr-diethyl, mefluidide, mefluidide-diolamine, mefluidide-potassium, megatomoic acid, menazon, mepanipyrim, meperfluthrin, mephenate, mephosfolan, mepiquat, mepiquat chloride, mepiquat pentaborate, mepronil, meptyldinocap, mercuric chloride, mercuric oxide, mercurous chloride, merphos, mesoprazine, mesosulfuron, mesosulfuron-methyl, mesotrione, mesulfen, mesulfenfos, metaflumizone, metalaxyl, metalaxyl-M, metaldehyde, metam, metam-ammonium, metamifop, metamitron, metam-potassium, metam-sodium, metazachlor, metazosulfuron, metazoxolon, metconazole, metepa, metflurazon, methabenzthiazuron, methacrifos, methalpropalin, methamidophos, methasulfocarb, methazole, methfuroxam, methidathion, methiobencarb, methiocarb, methiopyrisulfuron, methiotepa, methiozolin, methiuron, methocrotophos, methometon, methomyl, methoprene, methoprotryne, methoquin-butyl, methothrin, methoxychlor, methoxyfenozide, methoxyphenone, methyl apholate, methyl bromide, methyl eugenol, methyl iodide, methyl isothiocyanate, methylacetophos, methylchloroform, methyldymron, methylene chloride, methylmercury benzoate, methylmercury dicyandiamide, methylmercury pentachlorophenoxide, methylneodecanamide, metiram, metobenzuron, metobromuron, metofluthrin, metolachlor, metolcarb, metominostrobin, metosulam, metoxadiazone, metoxuron, metrafenone, metribuzin, metsulfovax, metsulfuron, metsulfuron-methyl, mevinphos, mexacarbate, mieshuan, milbemectin, milbemycin oxime, milneb, mipafox, mirex, MNAF, moguchun, molinate, molosultap, monalide, monisouron, monochloroacetic acid, monocrotophos, monolinuron, monosulfuron, monosulfuron-ester, monuron, monuron TCA, morfamquat, morfamquat dichloride, moroxydine, moroxydine hydrochloride, morphothion, morzid, moxidectin, MSMA, muscalure, myclobutanil, myclozolin, N-(ethylmercury)-p-toluenesulphonanilide, nabam, naftalofos, naled, naphthalene, naphthaleneacetamide, naphthalic anhydride, naphthoxyacetic acids, naproanilide, napropamide, naptalam, naptalam-sodium, natamycin, neburon, niclosamide, niclosamide-olamine, nicosulfuron, nicotine, nifluridide, nipyraclofen, nitenpyram, nithiazine, nitralin, nitrapyrin, nitrilacarb, nitrofen, nitrofluorfen, nitrostyrene, nitrothal-isopropyl, norbormide, norflurazon, nornicotine, noruron, novaluron, noviflumuron, nuarimol, OCH, octachlorodipropyl ether, octhilinone, ofurace, omethoate, orbencarb, orfralure, ortho-dichlorobenzene, orthosulfamuron, oryctalure, orysastrobin, oryzalin, osthol, ostramone, oxabetrinil, oxadiargyl, oxadiazon, oxadixyl, oxamate, oxamyl, oxapyrazon, oxapyrazon-dimolamine, oxapyrazon-sodium, oxasulfuron, oxaziclomefone, oxine-copper, oxolinic acid, oxpoconazole, oxpoconazole fumarate, oxycarboxin, oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyfluorfen, oxymatrine, oxytetracycline, oxytetracycline hydrochloride, paclobutrazol, paichongding, para-dichlorobenzene, parafluron, paraquat, paraquat dichloride, paraquat dimetilsulfate, parathion, parathion-methyl, parinol, pebulate, pefurazoate, pelargonic acid, penconazole, pencycuron, pendimethalin, penflufen, penfluron, penoxsulam, pentachlorophenol, pentanochlor, penthiopyrad, pentmethrin, pentoxazone, perfluidone, permethrin, pethoxamid, phenamacril, phenazine oxide, phenisopham, phenkapton, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenothrin, phenproxide, phenthoate, phenylmercuriurea, phenylmercury acetate, phenylmercury chloride, phenylmercury derivative of pyrocatechol, phenylmercury nitrate, phenylmercury salicylate, phorate, phosacetim, phosalone, phosdiphen, phosfolan, phosfolan-methyl, phosglycin, phosmet, phosnichlor, phosphamidon, phosphine, phosphocarb, phosphorus, phostin, phoxim, phoxim-methyl, phthalide, picloram, picloram-2-ethylhexyl, picloram-isoctyl, picloram-methyl, picloram-olamine, picloram-potassium, picloram-triethylammonium, picloram-tris(2-hydroxypropyl)ammonium, picolinafen, picoxystrobin, pindone, pindone-sodium, pinoxaden, piperalin, piperonyl butoxide, piperonyl cyclonene, piperophos, piproctanyl, piproctanyl bromide, piprotal, pirimetaphos, pirimicarb, pirimioxyphos, pirimiphos-ethyl, pirimiphos-methyl, plifenate, polycarbamate, polyoxins, polyoxorim, polyoxorim-zinc, polythialan, potassium arsenite, potassium azide, potassium cyanate, potassium gibberellate, potassium naphthenate, potassium polysulfide, potassium thiocyanate, potassium α-naphthaleneacetate, pp′-DDT, prallethrin, precocene I, precocene II, precocene III, pretilachlor, primidophos, primisulfuron, primisulfuron-methyl, probenazole, prochloraz, prochloraz-manganese, proclonol, procyazine, procymidone, prodiamine, profenofos, profluazol, profluralin, profluthrin, profoxydim, proglinazine, proglinazine-ethyl, prohexadione, prohexadione-calcium, prohydrojasmon, promacyl, promecarb, prometon, prometryn, promurit, propachlor, propamidine, propamidine dihydrochloride, propamocarb, propamocarb hydrochloride, propanil, propaphos, propaquizafop, propargite, proparthrin, propazine, propetamphos, propham, propiconazole, propineb, propisochlor, propoxur, propoxycarbazone, propoxycarbazone-sodium, propyl isome, propyrisulfuron, propyzamide, proquinazid, prosuler, prosulfalin, prosulfocarb, prosulfuron, prothidathion, prothiocarb, prothiocarb hydrochloride, prothioconazole, prothiofos, prothoate, protrifenbute, proxan, proxan-sodium, prynachlor, pydanon, pymetrozine, pyracarbolid, pyraclofos, pyraclonil, pyraclostrobin, pyraflufen, pyraflufen-ethyl, pyrafluprole, pyramat, pyrametostrobin, pyraoxystrobin, pyrasulfotole, pyrazolynate, pyrazophos, pyrazosulfuron, pyrazosulfuron-ethyl, pyrazothion, pyrazoxyfen, pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyribambenz-isopropyl, pyribambenz-propyl, pyribencarb, pyribenzoxim, pyributicarb, pyriclor, pyridaben, pyridafol, pyridalyl, pyridaphenthion, pyridate, pyridinitril, pyrifenox, pyrifluquinazon, pyriftalid, pyrimethanil, pyrimidifen, pyriminobac, pyriminobac-methyl, pyrimisulfan, pyrimitate, pyrinuron, pyriofenone, pyriprole, pyripropanol, pyriproxyfen, pyrithiobac, pyrithiobac-sodium, pyrolan, pyroquilon, pyroxasulfone, pyroxsulam, pyroxychlor, pyroxyfur, quassia, quinacetol, quinacetol sulfate, quinalphos, quinalphos-methyl, quinazamid, quinclorac, quinconazole, quinmerac, quinoclamine, quinonamid, quinothion, quinoxyfen, quintiofos, quintozene, quizalofop, quizalofop-ethyl, quizalofop-P, quizalofop-P-ethyl, quizalofop-P-tefuryl, quwenzhi, quyingding, rabenzazole, rafoxanide, rebemide, resmethrin, rhodethanil, rhodojaponin-III, ribavirin, rimsulfuron, rotenone, ryania, saflufenacil, saijunmao, saisentong, salicylanilide, sanguinarine, santonin, schradan, scilliroside, sebuthylazine, secbumeton, sedaxane, selamectin, semiamitraz, semiamitraz chloride, sesamex, sesamolin, sethoxydim, shuangjiaancaolin, siduron, siglure, silafluofen, silatrane, silica gel, silthiofam, simazine, simeconazole, simeton, simetryn, sintofen, SMA, S-metolachlor, sodium arsenite, sodium azide, sodium chlorate, sodium fluoride, sodium fluoroacetate, sodium hexafluorosilicate, sodium naphthenate, sodium orthophenylphenoxide, sodium pentachlorophenoxide, sodium polysulfide, sodium thiocyanate, sodium α-naphthaleneacetate, sophamide, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, spiroxamine, streptomycin, streptomycin sesquisulfate, strychnine, sulcatol, sulcofuron, sulcofuron-sodium, sulcotrione, sulfallate, sulfentrazone, sulfiram, sulfluramid, sulfometuron, sulfometuron-methyl, sulfosulfuron, sulfotep, sulfoxaflor, sulfoxide, sulfoxime, sulfur, sulfuric acid, sulfuryl fluoride, sulglycapin, sulprofos, sultropen, swep, tau-fluvalinate, tavron, tazimcarb, TCA, TCA-ammonium, TCA-calcium, TCA-ethadyl, TCA-magnesium, TCA-sodium, TDE, tebuconazole, tebufenozide, tebufenpyrad, tebufloquin, tebupirimfos, tebutam, tebuthiuron, tecloftalam, tecnazene, tecoram, teflubenzuron, tefluthrin, tefuryltrione, tembotrione, temephos, tepa, TEPP, tepraloxydim, terallethrin, terbacil, terbucarb, terbuchlor, terbufos, terbumeton, terbuthylazine, terbutryn, tetcyclacis, tetrachloroethane, tetrachlorvinphos, tetraconazole, tetradifon, tetrafluron, tetramethrin, tetramethylfluthrin, tetramine, tetranactin, tetrasul, thallium sulfate, thenylchlor, theta-cypermethrin, thiabendazole, thiacloprid, thiadifluor, thiamethoxam, thiapronil, thiazafluron, thiazopyr, thicrofos, thicyofen, thidiazimin, thidiazuron, thiencarbazone, thiencarbazone-methyl, thifensulfuron, thifensulfuron-methyl, thifluzamide, thiobencarb, thiocarboxime, thiochlorfenphim, thiocyclam, thiocyclam hydrochloride, thiocyclam oxalate, thiodiazole-copper, thiodicarb, thiofanox, thiofluoximate, thiohempa, thiomersal, thiometon, thionazin, thiophanate, thiophanate-methyl, thioquinox, thiosemicarbazide, thiosultap, thiosultap-diammonium, thiosultap-disodium, thiosultap-monosodium, thiotepa, thiram, thuringiensin, tiadinil, tiaojiean, tiocarbazil, tioclorim, tioxymid, tirpate, tolclofos-methyl, tolfenpyrad, tolylfluanid, tolylmercury acetate, topramezone, tralkoxydim, tralocythrin, tralomethrin, tralopyril, transfluthrin, transpermethrin, tretamine, triacontanol, triadimefon, triadimenol, triafamone, tri-allate, triamiphos, triapenthenol, triarathene, triarimol, triasulfuron, triazamate, triazbutil, triaziflam, triazophos, triazoxide, tribenuron, tribenuron-methyl, tribufos, tributyltin oxide, tricamba, trichlamide, trichlorfon, trichlormetaphos-3, trichloronat, triclopyr, triclopyr-butotyl, triclopyr-ethyl, triclopyr-triethylammonium, tricyclazole, tridemorph, tridiphane, trietazine, trifenmorph, trifenofos, trifloxystrobin, trifloxysulfuron, trifloxysulfuron-sodium, triflumizole, triflumuron, trifluralin, triflusulfuron, triflusulfuron-methyl, trifop, trifop-methyl, trifopsime, triforine, trihydroxytriazine, trimedlure, trimethacarb, trimeturon, trinexapac, trinexapac-ethyl, triprene, tripropindan, triptolide, tritac, triticonazole, tritosulfuron, trunc-call, uniconazole, uniconazole-P, urbacide, uredepa, valerate, validamycin, valifenalate, valone, vamidothion, vangard, vaniliprole, vernolate, vinclozolin, warfarin, warfarin-potassium, warfarin-sodium, xiaochongliulin, xinjunan, xiwojunan, XMC, xylachlor, xylenols, xylylcarb, yishijing, zarilamid, zeatin, zengxiaoan, zeta-cypermethrin, zinc naphthenate, zinc phosphide, zinc thiazole, zineb, ziram, zolaprofos, zoxamide, zuomihuanglong, α-chlorohydrin, α-ecdysone, α-multistriatin, and α-naphthaleneacetic acid.
 13. A composition according to claim 1 further comprising an agriculturally acceptable carrier.
 14. A composition according to claim 1 wherein said molecule is in the form of a pesticidally acceptable acid addition salt.
 15. A composition according to claim 1 wherein said molecule is in the form of a salt derivative.
 16. A composition according to claim 1 wherein said molecule is in the form a hydrate.
 17. A composition according to claim 1 wherein said molecule is in the form an ester derivative.
 18. A composition according to claim 1 wherein said molecule is in the form a crystal polymorph.
 19. A composition according to claim 1 wherein said molecule has a ²H in place of ¹H.
 20. A composition according to claim 1 wherein said molecule has a ¹⁴C in place of a ¹²C.
 21. A composition according to claim 1 further comprising a biopesticide.
 22. A composition according to claim 1 further comprising one or more of the following compounds: (a) 3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one; (b) 3-(4′-chloro-2,4-dimethyl[1,1′-biphenyl]-3-yl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one; (c) 4-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2(5H)-furanone; (d) 4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-furanone; (e) 3-chloro-N2-[(1S)-1-methyl-2-(methylsulfonyl)ethyl]-N1-[2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]-1,2-benzenedicarboxamide; (f) 2-cyano-N-ethyl-4-fluoro-3-methoxy-benenesulfonamide; (g) 2-cyano-N-ethyl-3-methoxy-benzenesulfonamide; (h) 2-cyano-3-difluoromethoxy-N-ethyl-4-fluoro-benzenesulfonamide; (i) 2-cyano-3-fluoromethoxy-N-ethyl-benzenesulfonamide; (j) 2-cyano-6-fluoro-3-methoxy-N,N-dimethyl-benzenesulfonamide; (k) 2-cyano-N-ethyl-6-fluoro-3-methoxy-N-methyl-benzenesulfonamide; (l) 2-cyano-3-difluoromethoxy-N,N-dimethylbenzenesulfon-amide; (m) 3-(difluoromethyl)-N-[2-(3,3-dimethylbutyl)phenyl]-1-methyl-1H-pyrazole-4-carboxamide; (n) N-ethyl-2,2-dimethylpropionamide-2-(2,6-dichloro-α,α,α-trifluoro-p-tolyl) hydrazone; (o) N-ethyl-2,2-dichloro-1-methylcyclopropane-carboxamide-2-(2,6-dichloro-α,α,α-trifluoro-p-tolyl) hydrazone nicotine; (p) O-{(E-)-[2-(4-chloro-phenyl)-2-cyano-1-(2-trifluoromethylphenyl)-vinyl]} S-methyl thiocarbonate; (q) (E)-N1-[(2-chloro-1,3-thiazol-5-ylmethyl)]-N2-cyano-N1-methylacetamidine; (r) 1-(6-chloropyridin-3-ylmethyl)-7-methyl-8-nitro-1,2,3,5,6,7-hexahydro-imidazo[1,2-a]pyridin-5-ol; (s) 4-[4-chlorophenyl-(2-butylidine-hydrazono)methyl)]phenyl mesylate; and (t) N-Ethyl-2,2-dichloro-1-methylcyclopropanecarboxamide-2-(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyl)hydrazone.
 23. A process of controlling pests comprising applying a composition according to claim 1, to an area in an amount sufficient to control such pest.
 24. A composition according to claim 1 further comprising a seed.
 25. A composition according to claim 1 further comprising a seed that has been genetically modified to express one or more specialized traits.
 26. A composition according to claim 1 wherein said composition is encapsulated inside, or placed on the surface of, a capsule.
 27. A composition according to claim 1 wherein said composition is encapsulated inside, or placed on the surface of, a capsule, wherein said capsule has a diameter of about 100-900 nanometers or about 10-900 microns.
 28. A composition according to claim 1 where said composition further comprises ammonium sulfate.
 29. A process comprising applying a composition according to claim 1, to an area to control a pest, in an amount sufficient to control such pest.
 30. A process according to claim 29 wherein said pest is selected from the group consisting of beetles, earwigs, cockroaches, flies, aphids, scales, whiteflies, leafhoppers, ants, wasps, termites, moths, butterflies, lice, grasshoppers, locusts, crickets, fleas, thrips, bristletails, mites, ticks, nematodes, and symphylans.
 31. A process according to claim 29 wherein said pest is from phyla Nematoda or Arthropoda.
 32. A process according to claim 29 wherein said pest is from subphyla Chelicerata, Myriapoda, or Hexapoda.
 33. A process according to claim 29 wherein said pest is from class of Arachnida, Symphyla, or Insecta.
 34. A process according to claim 29 wherein said pest is from, order Anoplura, order Coleoptera, order Dermaptera, order Blattaria, order Diptera, order Hemiptera, order Hymenoptera, order Isoptera, order Lepidoptera, order Mallophaga, order orthoptera, order Siphonaptera, order Thysanoptera, order Thysanura, order Acarina, or order Symphyla.
 35. A process according to claim 29 wherein said pest is Beet Army Worm, Corn Earworm, or Cabbage Looper.
 36. A process according to claim 29 wherein said amount is from about 0.01 grams per hectare to about 5000 grams per hectare.
 37. A process according to claim 29 wherein said amount is from about 0.1 grams per hectare to about 500 grams per hectare.
 38. A process according to claim 29 wherein said amount is from about 1 gram per hectare to about 50 grams per hectare.
 39. A process according to claim 29 wherein said area is an area where apples, corn, cotton, soybeans, canola, wheat, rice, sorghum, barley, oats, potatoes, oranges, alfalfa, lettuce, strawberries, tomatoes, peppers, crucifers, pears, tobacco, almonds, sugar beets, or beans, are growing, or the seeds thereof are going to be planted.
 40. A process according to claim 29 further comprising applying said composition to a genetically modified plant that has been genetically modified to express one or more specialized traits.
 41. A process of controlling endoparasites, ectoparasites, or both, comprising orally administering; or topically applying; a composition according to claim 1, to a non-human animal.
 42. A process of enhancing a plant's health, yield, vigor, quality, or tolerance, at a time when pest activity is low comprising applying a composition according to claim 1 to a plant. 